JP2004298086A

JP2004298086A - Method for detecting gene based on human mitochondrial gene mutation

Info

Publication number: JP2004298086A
Application number: JP2003095200A
Authority: JP
Inventors: Masatsugu Tanaka; 雅嗣田中
Original assignee: GENOME SCIENCE LAB CO Ltd; GENOME SCIENCE LABORATORIES CO Ltd; Gifu International Institute of Biotechnology
Current assignee: GENOME SCIENCE LAB CO Ltd; GENOME SCIENCE LABORATORIES CO Ltd; Gifu International Institute of Biotechnology
Priority date: 2003-03-31
Filing date: 2003-03-31
Publication date: 2004-10-28

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for detecting a gene, giving useful information for determination on whether or not some persons may suffer from Parkinson's disease or whether or not some persons may become health and long-lived based on searching mitochondrial genomic polymorphisms associated with persons of 100-year old and patients with Parkinson's disease. <P>SOLUTION: A mitochondrial genomic whole base sequence is analyzed by a direct base sequence determination method in each of 96 persons of 100-year old and patients with Parkinson's disease. Consequently, a total of 557 mutations are confirmed in the patients with Parkinson's disease[ 348 mutations in the coding region( 244 multiple substitutions and 104 non-multiple substitutions )] and a total of 519 mutations in the persons of 100-year old[ 327 mutations in the coding region( 231 multiple substitutions and 96 non-multiple substitutions )]. Analysis of these mutations in details enables mutations involved in health and longevity to be identified. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【０００１】
【発明の属する技術分野】
本発明は、ヒトミトコンドリアＤＮＡ（ｍｔＤＮＡ）の多型に関するものであり、そのｍｔＤＮＡ多型を利用して、ある人がパーキンソン病となり得るか否かに関して有用な情報を与える検出方法、ある人が健康長寿となり得るか否かに関して有用な情報を与える検出方法、或いは個人識別方法（例えば、法医学、親子鑑定、疫学調査、考古学調査等）などに応用することができる。
【０００２】
【従来の技術】
パーキンソン病は、遺伝的素因を含む多因子性の疾患であると考えられている。このパーキンソン病に関する遺伝学の研究や候補遺伝子の解析は、ヒト遺伝子解析プログラムの進展とも伴って、飛躍的な進歩を見せている。
一方、満年齢で百歳を越える百寿者のように、健康で長寿を享受している者も少なくない。これらの百寿者では、特異的な遺伝子多型を備えている可能性がある。
【０００３】
ヒトミトコンドリア遺伝子（以下、ｍｔＤＮＡという）は、ミトコンドリア中に存在し、母系性遺伝を行うことが知られている。ミトコンドリアでは、主としてエネルギー代謝に関する反応が行われていることから、健康長寿な者との関連、及び一部のパーキンソン病との関連が考えられる。
本発明者らは、継続してｍｔＤＮＡの多型に関する研究を行っているが（例えば、特開平１１−１１３５９７）、ｍｔＤＮＡの多型と健康長寿者、及びパーキンソン病との間の詳細な関係を解析した従来技術については、確認していない。
【特許文献１】特開平１１−１１３５９７号公報
【０００４】
【発明が解決しようとする課題】
ゲノム多型は、人種や民族により異なるので、各々の人種や民族でパーキンソン病に関連したミトコンドリアゲノム多型データベース、及び健康著寿に関するミトコンドリアゲノム多型データベースの構築をすることは重要である。
本発明は、上記した事情に鑑みてなされたものであり、その目的はパーキンソン病患者と長寿者とのミトコンドリアゲノム多型を探索することにより、パーキンソン病の予防・診断に貢献すること、及び健康長寿に関連する多型を見出すことにあり、また他の目的は、ミトコンドリアゲノム多型に基づいた個人識別方法を提供することにある。
【０００５】
【課題を解決するための手段、発明の作用、及び発明の効果】
本発明者らは、それぞれ９６名づつのパーキンソン病患者、及び百寿者（満年齢で９９．１歳以上の寿命を得た者）のヒトミトコンドリアＤＮＡの全塩基配列（１６５６９塩基対）を全て解読し、変異（置換、欠失、付加）を解析することにより、基本的には本発明を完成するに至った。
両群のヒトミトコンドリアＤＮＡの変異を比較することにより、（１）パーキンソン病となる危険性の高い者、（２）長寿と成り得る可能性が高い者などを判断するための資料を与えることができる。また、両群において検出された変異に基づいて、個人識別を行うこともできる。
【０００６】
すなわち、上記の課題を解決するために第１の発明は、ヒトミトコンドリアＤＮＡにおいて、４２ｉｎｓ−Ｃ，Ｔ６３Ｃ，Ｃ６４Ｔ，６６ｄｅｌ−Ｇ，Ｇ６８Ａ，Ａ７３Ｇ，Ａ９３Ｇ，Ｇ９４Ａ，Ｇ１０３Ａ，Ｔ１３１Ｃ，Ｔ１４６Ｃ，Ｃ１５０Ｔ，Ｃ１５１Ｔ，Ｔ１５２Ｃ，Ａ１５３Ｇ，Ａ１８３Ｇ，Ｇ１８５Ａ，Ａ１８９Ｇ，１９０ｉｎｓ−Ａ，Ａ１９１Ｇ，Ａ１９３Ｇ，Ｃ１９４Ｔ，Ｔ１９５Ｃ，Ｔ１９６Ｃ，Ｃ１９８Ｔ，Ｔ１９９Ｃ，Ａ２００Ｇ，Ａ２０２Ｇ，Ｇ２０３Ａ，Ｔ２０４Ｃ，Ｇ２０７Ａ，Ａ２１０Ｇ，Ａ２１１Ｇ，Ａ２１４Ｇ，Ｇ２２８Ａ，Ａ２３５Ｇ，２４８ｄｅｌ−Ａ，Ｔ２５２Ｃ，Ａ２５７Ｇ，Ｇ２６０Ａ，Ａ２６３Ｇ，Ｔ２７９Ｃ，Ｃ２８０Ｔ，Ａ２８１Ｇ，Ａ２８４Ｇ，２８６ｄｅｌ−Ａ，２８７ｄｅｌ−Ａ，Ｃ２９８Ｔ，３１０ｉｎｓ−Ｃ，Ｃ３２５Ｔ，Ｃ３４８Ｇ，Ｃ３４８Ｔ，Ａ３５１Ｃ，Ａ３６８Ｇ，Ｇ３８０Ｃ，Ｃ３８２Ｇ，Ａ３８５Ｔ，Ｔ４０８Ｇ，Ｔ４０８Ａ，Ｃ４３１Ｔ，Ｃ４４１Ｔ，４５１ｉｎｓ−Ｔ，Ｃ４５６Ｔ，Ｃ４８１Ｔ，Ｔ４８９Ｃ，Ｇ４９９Ａ，Ｔ５０４Ｃ，Ｃ５０６Ｔ，Ｇ５１３Ａ，Ｃ５３０Ｔ，Ａ５３３Ｇ，５４０ｉｎｓ−Ｃ，Ａ５４６Ｇ，Ｃ５５２Ｔ，Ａ６６３Ｇ，Ｔ６８１Ｃ，Ｇ７０９Ａ，Ｃ７５２Ｔ，Ａ８２７Ｇ，Ａ８５６Ｇ，Ｔ９６１Ｃ，Ｃ９８３Ｔ，Ｃ９８４Ｔ，Ａ９９８Ｇ，Ａ１０４１Ｇ，Ｃ１０４８Ｔ，Ｔ１１０７Ｃ，Ａ１１１８Ｇ，Ｔ１１１９Ｃ，Ａ１１４８Ｇ，Ｇ１２１１Ａ，Ｃ１３１０Ｔ，Ａ１３８２Ｃ，Ｔ１４２０Ｃ，Ａ１４３８Ｇ，Ｇ１４４２Ａ，Ｇ１５９８Ａ，Ｇ１６６４Ａ，Ｇ１７０９Ａ，Ｇ１７１９Ａ，Ｃ１７３４Ｔ，Ａ１７３６Ｇ，Ｔ１８１９Ｃ，Ｔ１８２２Ｃ，Ｇ１８８８Ａ，Ｔ１９７７Ｃ，２１５０ｉｎｓ−Ａ，Ａ２１７８Ｇ，Ａ２２２０Ｇ，Ａ２２４６Ｇ，Ｃ２２６３Ａ，Ｔ２３３０Ｃ，Ｔ２４１６Ｃ，Ｔ２６２６Ｃ，Ａ２７０６Ｇ，Ｃ２７６６Ｔ，Ｃ２７７２Ｔ，Ｇ２８３１Ａ，Ｃ２８３５Ｔ，Ｔ２８６３Ｃ，Ｔ２８８７Ｃ，Ｇ３０１０Ａ，３１０６ｄｅｌ−Ｃ，３１０７ｄｅｌ−Ｃ，Ａ３１４５Ｇ，Ｃ３２０４Ｔ，Ｃ３２０６Ｔ，Ａ３２２１Ｇ，Ｔ３２７８Ｃ，Ｇ３３１６Ａ，Ａ３３２７Ｇ，Ｔ３３３６Ｃ，Ｔ３３３８Ｃ，Ｇ３３９１Ａ，Ｔ３３９４Ｃ，Ａ３３９７Ｇ，Ｔ３４２３Ｃ，Ｃ３４４２Ｔ，Ｔ３４５６Ｃ，Ｇ３４９６Ｔ，Ｃ３４９７Ｔ，Ａ３５２０Ｇ，Ａ３５３７Ｇ，Ｔ３５５２Ｃ，Ｔ３５５２Ａ，Ｇ３５９１Ａ，Ｔ３６４４Ｃ，Ｃ３６９６Ｔ，Ａ３７２０Ｇ，Ａ３７５９Ｇ，Ａ３７６８Ｇ，Ｔ３８２６Ｃ，Ａ３８７３Ｇ，Ｇ３８８２Ａ，Ｃ３９６０Ｔ，Ｃ３９６３Ａ，Ｃ３９７０Ｔ，Ｔ４０４７Ｃ，Ｇ４０４８Ａ，Ｔ４０６２Ｃ，Ｃ４０７１Ｔ，Ｃ４０８６Ｔ，Ｇ４０９２Ａ，Ｇ４１１３Ａ，Ｔ４１１７Ｃ，Ａ４１３１Ｇ，Ａ４１６４Ｇ，Ａ４２０３Ｇ，Ｔ４２０９Ｃ，Ｔ４２３２Ｃ，Ｔ４２４８Ｃ，Ｃ４２５１Ｔ，Ａ４３１０Ｇ，Ａ４３４３Ｇ，Ｔ４３８６Ｃ，Ｃ４３９４Ｔ，Ｇ４４９１Ａ，Ｃ４５０５Ｔ，Ｇ４５４１Ｔ，Ｔ４６１２Ｃ，Ｇ４６５５Ａ，Ｇ４６５９Ａ，Ｃ４６７０Ｔ，Ｔ４６８８Ｃ，Ｔ４７０５Ｃ，Ａ４７１５Ｇ，Ａ４７３２Ｇ，Ｔ４７３６Ｃ，Ｔ４７４２Ｃ，Ａ４７６９Ｇ，Ａ４７９３Ｇ，Ｇ４８２０Ａ，Ａ４８２４Ｇ，Ａ４８３３Ｇ，Ｃ４８５０Ｔ，Ｔ４８５９Ｃ，Ｃ４８８３Ｔ，Ａ４８９５Ｇ，Ｇ４９２４Ａ，Ｃ４９２６Ｔ，Ａ４９５８Ｇ，Ｔ５０４８Ｃ，Ｃ５０４９Ｔ，Ｇ５０５４Ａ，Ｔ５１０８Ｃ，Ａ５１２７Ｇ，Ａ５１２８Ｇ，Ｇ５１４７Ａ，Ａ５１５３Ｇ，Ｃ５１７８Ａ，Ｔ５２０１Ｃ，Ｇ５２３１Ａ，Ｇ５２３７Ａ，Ａ５２４０Ｇ，Ｇ５２６１Ａ，Ｃ５２６３Ｔ，Ａ５３０１Ｇ，Ａ５３５１Ｃ，Ａ５３５１Ｇ，Ｃ５３７９Ｔ，Ｇ５４１７Ａ，Ａ５４４１Ｇ，Ｔ５４４２Ｃ，Ｇ５４６０Ａ，Ｔ５４６５Ｃ，Ｇ５４７１Ａ，Ｔ５４９２Ｃ，Ａ５５３９Ｇ，Ｃ５６０１Ｔ，Ｔ５６２８Ｃ，Ｔ５６５５Ｃ，Ｇ５７４４Ａ，Ｇ５７７３Ａ，Ｔ５７８８Ｃ，Ｇ５８２１Ａ，Ｔ５８２６Ｃ，Ｔ５８２６Ｃ，Ａ５８９４Ｇ，Ａ５９００Ｃ，Ａ５９５１Ｇ，Ｔ５９６４Ｃ，Ｇ５９７９Ａ，Ｇ６０１８Ａ，Ｇ６０２３Ａ，Ｇ６０２６Ａ，Ａ６０３９Ｇ，Ｃ６０５３Ｔ，Ａ６１４６Ｇ，Ｇ６１７９Ａ，Ｔ６１８５Ｃ，Ｔ６２２１Ｃ，Ｃ６２４２Ｔ，Ｔ６２５３Ｃ，Ｇ６２６１Ａ，Ｔ６２７８Ｃ，Ａ６２９９Ｇ，Ｇ６３０５Ａ，Ａ６３３２Ｇ，Ｇ６３８３Ａ，Ｔ６３９２Ｃ，Ｃ６４１０Ｔ，Ｔ６４１３Ｃ，Ａ６４１６Ｇ，Ｃ６４５２Ｔ，Ｃ６４５５Ｔ，Ｃ６４８３Ｔ，Ｔ６５１２Ｃ，Ｔ６５２４Ｃ，Ａ６５３３Ｇ，Ｃ６５４２Ｔ，Ｃ６５６９Ａ，Ａ６５７５Ｇ，Ｔ６６１４Ｃ，Ｔ６６２０Ｃ，Ｔ６６４１Ｃ，Ｃ６６４４Ｔ，Ｔ６６７１Ｃ，Ｔ６６８０Ｃ，Ｃ６６８９Ｔ，Ａ６６９８Ｇ，Ｔ６７１９Ｃ，Ａ６７３７Ｇ，Ａ６７５２Ｇ，Ｃ６７６１Ｔ，Ｇ６８９９Ａ，Ｇ６９６２Ａ，Ｃ６９８３Ｔ，Ｃ７０２８Ｔ，Ｔ７０５８Ｃ，Ｔ７１４２Ｃ，Ａ７１４６Ｇ，Ｔ７１９１Ｃ，Ｃ７１９６Ａ，Ｃ７２１４Ｔ，Ｔ７２２０Ｃ，Ｃ７２３２Ｔ，Ｃ７２３５Ｔ，Ｃ７２４４Ｔ，Ｃ７２５６Ｔ，Ｔ７２５８Ｃ，Ｔ７２７０Ｃ，Ａ７３５２Ｔ，Ｔ７３８９Ｃ，Ａ７４０３Ｇ，Ｃ７４９２Ｔ，７５０２ｄｅｌ−Ｃ，Ｇ７５２１Ａ，Ｇ７５９８Ａ，Ｇ７６００Ａ，Ａ７６７３Ｇ，Ｔ７６８４Ｃ，Ｔ７７３８Ｃ，Ａ７７５５Ｇ，Ｃ７７７４Ｔ，Ｃ７８１０Ｔ，Ａ７８２２Ｇ，Ｇ７８５３Ａ，Ｔ７８６１Ｃ，Ｃ７８６７Ｔ，Ｃ７８６８Ｔ，Ｃ７８９１Ｔ，Ｃ７９０９Ｔ，Ｇ７９１２Ａ，Ｃ７９２７Ｔ，Ｔ７９６１Ｃ，Ｇ８０２０Ａ，Ａ８０２１Ｇ，Ｔ８０６３Ｃ，Ａ８０７１Ｇ，Ａ８０７４Ｇ，Ｃ８１４０Ｔ，Ａ８１４９Ｇ，Ｔ８１６７Ａ，Ｔ８１６７Ｃ，Ａ８１８８Ｇ，Ｔ８２００Ｃ，Ｃ８２０３Ｔ，Ｇ８２０６Ａ，Ａ８２２５Ｇ，Ｔ８２２７Ｃ，Ｇ８２５１Ａ，Ｔ８２６５Ｃ，Ｃ８２７０Ｔ，Ｇ８２９０Ａ，Ａ８２９１Ｇ，Ｃ８２９７Ｇ，Ａ８３０８Ｇ，Ｔ８３８３Ｃ，Ｇ８３９２Ａ，Ａ８４１３Ｇ，Ｃ８４１４Ｔ，Ｔ８４１９Ｃ，Ｃ８４２９Ａ，Ｔ８４５０Ｃ，Ｃ８４５５Ｔ，Ｃ８４６１Ｔ，Ａ８４７０Ｇ，Ｔ８４７３Ｃ，Ａ８４８９Ｇ，Ａ８５３７Ｇ，Ａ８５３７Ｇ，Ｇ８５５７Ａ，Ｇ８５５７Ａ，Ａ８５６３Ｇ，Ａ８５６３Ｇ，Ｇ８５７２Ａ，Ｇ８５８４Ａ，Ｃ８５９５Ｔ，Ｔ８６１０Ｃ，Ｔ８６５４Ｃ，Ａ８６６４Ｇ，Ｃ８６８４Ｔ，Ａ８７０１Ｇ，Ｔ８７６２Ｃ，Ａ８７８４Ｇ，Ｃ８７８８Ｔ，Ｃ８７９４Ｔ，Ａ８８１２Ｇ，Ｃ８８２９Ｔ，Ｃ８８４４Ｔ，Ｇ８８５４Ａ，Ａ８８６０Ｇ，Ａ８８９４Ｔ，Ｃ８９０５Ａ，Ａ８９２９Ｇ，Ｃ８９６４Ｔ，Ｇ８９９４Ａ，Ｔ９０１７Ｃ，Ａ９０４１Ｇ，Ｇ９０５３Ａ，Ａ９０６９Ｇ，Ｔ９０８４Ｃ，Ｔ９０９０Ｃ，Ｃ９０９９Ａ，Ａ９１１５Ｇ，Ｇ９１２３Ａ，Ｔ９１２８Ｃ，Ｃ９１２９Ｔ，Ｔ９１６５Ｃ，Ｔ９１７４Ｃ，Ａ９１８０Ｇ，Ａ９２４２Ｇ，Ａ９２８８Ｇ，Ｃ９２９３Ｔ，Ｃ９２９６Ｔ，Ａ９２９９Ｇ，Ｇ９３０５Ａ，Ａ９３４１Ｔ，Ａ９３７７Ｇ，Ｔ９３８６Ｃ，Ｃ９４３１Ｔ，Ｇ９４７７Ａ，Ｔ９４７９Ｃ，Ａ９４９４Ｇ，Ｃ９５３６Ｔ，Ｔ９５４０Ｃ，Ａ９５４５Ｇ，Ｇ９５４８Ａ，Ｇ９５７５Ａ，Ｇ９６１２Ａ，Ａ９６６７Ｇ，Ｔ９７５０Ｃ，Ｇ９７５５Ａ，Ｇ９８０４Ａ，Ｃ９８１２Ｔ，Ｔ９８２４Ｃ，Ｔ９８２４Ａ，Ｔ９８３３Ｃ，Ｔ９８３６Ｇ，Ａ９８４３Ｇ，Ｇ９９２１Ａ，Ｇ９９３２Ａ，Ｔ９９３８Ｃ，Ｔ９９５０Ｃ，Ｔ９９５９Ｃ，Ｇ９９６２Ａ，Ｔ９９７７Ｃ，Ｔ１００８４Ｃ，Ｃ１０１０４Ｔ，Ｇ１０１７２Ａ，Ｃ１０１８１Ｔ，Ｔ１０２３８Ｃ，Ｔ１０２７４Ｃ，Ｇ１０３１０Ａ，Ｔ１０３４５Ｃ，Ｇ１０３７３Ａ，Ａ１０３９７Ｇ，Ａ１０３９８Ｇ，Ｃ１０４００Ｔ，Ｔ１０４１０Ｃ，Ａ１０４１１Ｇ，Ｔ１０６０９Ｃ，Ｃ１０６３７Ｔ，Ｇ１０６４６Ａ，Ａ１０７５０Ｇ，Ｔ１０７９０Ｃ，Ｇ１０８０１Ａ，Ｔ１０８７３Ｃ，Ａ１０８７６Ｇ，Ｔ１０９１５Ｃ，Ｃ１０９５４Ｔ，Ａ１０９７２Ｇ，Ｃ１０９７６Ｔ，Ｇ１１０１６Ａ，Ｔ１１０１７Ｃ，Ａ１１０２０Ｇ，Ｃ１１０５９Ｔ，Ａ１１０８４Ｇ，Ｔ１１０８７Ｃ，Ｔ１１１１３Ｃ，Ｃ１１１４６Ｔ，Ｇ１１１４９Ａ，Ｃ１１１５１Ｔ，Ａ１１１６７Ｇ，Ｃ１１２１５Ｔ，Ｔ１１４３７Ｃ，Ａ１１５３０Ｇ，Ｃ１１５３６Ｔ，Ｃ１１６４７Ｔ，Ｃ１１６６５Ｔ，Ｇ１１６９６Ａ，Ｔ１１７０１Ｃ，Ｇ１１７１９Ａ，Ｔ１１７２２Ｃ，Ｔ１１７７０Ｃ，Ｔ１１８５４Ｃ，Ｇ１１９１４Ａ，Ｔ１１９４４Ｃ，Ａ１１９５９Ｇ，Ｇ１１９６９Ａ，Ｇ１２００７Ａ，Ａ１２０２６Ｇ，Ａ１２０３０Ｇ，Ａ１２０４０Ｇ，Ｃ１２０８４Ｔ，Ｃ１２０８８Ｔ，Ｔ１２０９１Ｃ，Ｃ１２０９２Ａ，Ｇ１２１９２Ａ，Ａ１２２１０Ｇ，Ａ１２２３４Ｇ，Ｔ１２３１１Ｃ，Ｔ１２３５４Ｃ，Ａ１２３５８Ｇ，Ａ１２３６１Ｇ，Ｇ１２３７２Ａ，Ｔ１２３９６Ｃ，Ａ１２３９７Ｇ，Ｃ１２４０５Ｔ，Ｇ１２４０６Ａ，Ｔ１２４０８Ｃ，Ｔ１２４６８Ｃ，Ｇ１２６２２Ａ，Ｇ１２６３０Ａ，Ｃ１２６３３Ｔ，Ａ１２６３４Ｇ，Ｇ１２６５１Ｃ，Ｇ１２６５１Ａ，Ｃ１２７０５Ｔ，Ｇ１２７７１Ａ，Ｔ１２８０４Ｃ，Ｔ１２８１１Ｃ，Ｃ１２８１６Ｔ，Ａ１２８３４Ｇ，Ｔ１２８８０Ｃ，Ｃ１２８８２Ｔ，Ｃ１３０１１Ｔ，Ａ１３０５０Ｇ，Ｃ１３０５３Ｇ，Ａ１３０５７Ｇ，Ａ１３１０４Ｇ，Ａ１３１０５Ｇ，Ｃ１３１１０Ｔ，Ｇ１３１３５Ａ，Ｔ１３１４３Ｃ，Ｔ１３２１５Ｃ，Ａ１３２２１Ｇ，Ｔ１３２２４Ｃ，Ｇ１３２２５Ａ，Ｃ１３２５１Ｔ，Ａ１３２６３Ｇ，Ａ１３２６９Ｇ，Ａ１３２７８Ｇ，Ｔ１３２８１Ｃ，Ｃ１３３３８Ｔ，Ｇ１３３５９Ａ，Ｃ１３３８３Ｔ，Ａ１３３９５Ｇ，Ａ１３４１３Ｇ，Ａ１３４３４Ｇ，Ｔ１３４６１Ｃ，Ｔ１３５００Ｃ，Ａ１３５６３Ｇ，Ｇ１３５９０Ａ，Ａ１３６０６Ｇ，Ａ１３６１４Ｇ，Ｔ１３６１７Ｃ，Ａ１３６２９Ｇ，Ａ１３６５１Ｇ，Ｃ１３６９５Ａ，Ｇ１３７０８Ａ，Ｇ１３７５９Ａ，Ｔ１３７６８Ｃ，Ｇ１３８１０Ａ，Ａ１３８２７Ｇ，Ｔ１３８７９Ｃ，Ａ１３８８７Ｇ，Ｇ１３９２８Ａ，Ｇ１３９２８Ｃ，Ａ１４００１Ｇ，Ａ１４００２Ｇ，Ｇ１４０１６Ａ，Ａ１４０５３Ｇ，Ｃ１４０８２Ｔ，Ａ１４０９１Ｇ，Ａ１４１３３Ｇ，Ｃ１４１４９Ｔ，Ｃ１４１５８Ｔ，Ａ１４１６１Ｇ，Ｇ１４１６２Ａ，Ｔ１４１８０Ｃ，Ａ１４１８５Ｔ，Ｇ１４１９８Ａ，Ｔ１４２００Ｃ，Ｇ１４２２６Ａ，Ｃ１４２８１Ｔ，Ｃ１４２８１Ｇ，Ｔ１４２８７Ｃ，Ｔ１４３０８Ｃ，Ｔ１４３１８Ｃ，Ｔ１４３２５Ｃ，Ｇ１４３６４Ａ，Ｃ１４３６５Ｇ，Ｔ１４３７１Ｃ，Ｔ１４３８６Ｃ，Ｃ１４３８９Ｔ，Ａ１４４１７Ｇ，Ｔ１４４７０Ｃ，Ｇ１４４７６Ａ，Ｇ１４５４４Ａ，Ａ１４５４８Ｇ，Ｃ１４５６２Ｇ，Ｇ１４５６９Ａ，Ａ１４５８２Ｇ，Ａ１４６０５Ｇ，Ｃ１４６６８Ｔ，Ａ１４６９３Ｇ，Ａ１４６９６Ｇ，Ａ１４７５０Ｇ，Ｃ１４７６６Ｔ，Ｔ１４７８３Ｃ，Ｃ１４８６７Ｔ，Ｃ１４９４４Ｔ，Ｔ１４９７９Ｃ，Ｇ１５０４３Ａ，Ｔ１５０６７Ｃ，Ｇ１５１４８Ａ，Ａ１５２１８Ｇ，Ｃ１５２２３Ｔ，Ａ１５２３５Ｇ，Ａ１５２３６Ｇ，Ｇ１５３０１Ａ，Ｇ１５３１４Ａ，Ｇ１５３２３Ａ，Ａ１５３２６Ｇ，Ｃ１５３３１Ａ，Ｇ１５３４６Ａ，Ｇ１５３５５Ａ，Ｔ１５４４０Ｃ，Ｔ１５４７９Ｃ，Ａ１５４８７Ｔ，Ｇ１５４９７Ａ，Ｃ１５５０８Ｔ，Ｃ１５５１８Ｔ，Ａ１５５２４Ｇ，Ｃ１５５３５Ｔ，Ａ１５６６２Ｇ，Ｔ１５６７０Ｃ，Ａ１５７２４Ｇ，Ａ１５７５８Ｇ，Ｔ１５７８４Ｃ，Ｔ１５８５０Ｃ，Ａ１５８５１Ｇ，Ａ１５８６０Ｇ，Ａ１５８７４Ｇ，Ｇ１５８８４Ａ，Ａ１５９２４Ｇ，Ｇ１５９２７Ａ，Ｔ１５９４０− ，Ｔ１５９４１Ｃ，Ａ１５９５１Ｇ，Ａ１５９５４Ｇ，Ａ１５９７４Ｇ，Ｇ１６０００Ａ，Ａ１６０３７Ｇ，Ａ１６０５１Ｇ，Ｔ１６０７５Ｃ，Ｔ１６０８６Ｃ，Ｔ１６０９２Ｃ，Ｔ１６０９３Ｃ，Ｔ１６０９４Ｃ，Ｃ１６１１１Ｔ，Ｔ１６１２６Ｃ，Ｇ１６１２９Ａ，Ｔ１６１３６Ｃ，Ｔ１６１４０Ｃ，Ｇ１６１４５Ａ，Ｔ１６１５４Ｃ，Ａ１６１６２Ｇ，Ａ１６１６４Ｇ，Ｃ１６１６８Ｔ，Ｃ１６１６９Ｔ，Ｔ１６１７２Ｃ，Ｃ１６１７３Ｔ，Ｃ１６１７４Ｔ，Ｃ１６１７６Ｔ，Ａ１６１８３Ｃ，Ｔ１６１８９Ｃ，Ｃ１６２０１Ｔ，Ｔ１６２０９Ｃ，Ｃ１６２１４Ｇ，Ａ１６２１５Ｇ，Ａ１６２１６Ｇ，Ｔ１６２１７Ｃ，Ｃ１６２２３Ｔ，Ｔ１６２２４Ｃ，Ａ１６２２７Ｇ，Ｃ１６２３２Ａ，Ｃ１６２３４Ｔ，Ａ１６２３５Ｇ，Ａ１６２４０Ｇ，Ｔ１６２４３Ｃ，Ｇ１６２４４Ａ，Ｃ１６２４５Ｔ，Ｔ１６２４９Ｃ，Ａ１６２５２Ｃ，Ａ１６２５４Ｇ，Ｃ１６２５６Ｔ，Ｃ１６２５７Ａ，Ｃ１６２５７Ｔ，Ａ１６２５８Ｔ，１６２５８ｉｎｓ−Ｃ，Ｃ１６２６０Ｔ，Ｃ１６２６１Ｔ，Ｔ１６２６３Ｃ，Ａ１６２６５Ｇ，Ｃ１６２６６Ｔ，Ｃ１６２６６Ａ，Ｃ１６２６８Ｔ，Ａ１６２６９Ｇ，Ｃ１６２７０Ｔ，Ｇ１６２７４Ａ，Ｃ１６２７８Ｔ，Ａ１６２８４Ｇ，Ｃ１６２８７Ｔ，Ｔ１６２８８Ｃ，Ｃ１６２９０Ｔ，Ｃ１６２９１Ｔ，Ｃ１６２９１Ｇ，Ｃ１６２９２Ｔ，Ｃ１６２９２Ｇ，Ｃ１６２９４Ｔ，Ｃ１６２９５Ｔ，Ｃ１６２９６Ｔ，Ｔ１６２９７Ｃ，１６２９８ｉｎｓ−Ａ，Ｔ１６２９８Ｃ，Ａ１６２９９Ｇ，Ａ１６３００Ｇ，Ａ１６３０２Ｇ，Ｔ１６３０４Ｃ，Ａ１６３０９Ｇ，Ｔ１６３１１Ｃ，Ａ１６３１６Ｇ，Ａ１６３１７Ｇ，Ａ１６３１８Ｔ，Ｇ１６３１９Ａ，Ｃ１６３２０Ｔ，Ｔ１６３２４Ｃ，Ｔ１６３２５Ｃ，Ｃ１６３２７Ｔ，Ｔ１６３４２Ｃ，Ｃ１６３４４Ｔ，Ｔ１６３５２Ｃ，Ｃ１６３５５Ｔ，Ｔ１６３５６Ｃ，Ｔ１６３５７Ｃ，Ｃ１６３６０Ｔ，Ｔ１６３６２Ｃ，Ａ１６３６７Ｃ，Ｔ１６３６８Ｃ，Ｇ１６３７３Ａ，Ｔ１６３８１Ｃ，Ｇ１６３９０Ａ，Ａ１６３９９Ｇ，Ｃ１６４００Ｔ，Ｇ１６４５６Ｃ，Ａ１６４６３Ｇ，Ａ１６４９７Ｇ，Ｔ１６５１９Ｃ，Ａ１６５２３Ｇ，Ｃ１６５２７Ｔのうちの少なくとも一つ、または二つ以上の塩基の変異に基づいて、個人識別することを特徴とするヒトミトコンドリア遺伝子変異に基づく個人識別法である。
【０００７】
パーキンソン病患者群においては５５７個の変異が、百寿者群においては５１９個の変異が確認された。上記の７６２個の変異は、それらの重複ヶ所を除いた全てのものである。
本発明において、変異とは、いわゆる「改訂版ケンブリッジ標準配列」、或いは本発明者らが見出した日本人におけるコンセンサスシークエンス（ＪＣＳ：表２を参照）に比べて、特定の塩基が変異していることを意味している。なお、本明細書中において、「変異」とは、塩基の置換、挿入、または欠失を含む。
また、本明細書中においては、塩基置換については、▲１▼数字の後ろに二つの英文字が矢印（→）を挟んだ状態、又は▲２▼２種類の英文字が数字を挟んだ状態で示している。上記▲１▼の場合には、数字は塩基置換が行われた位置を示し、始めの英文字が置換前の塩基を後の英文字が置換後の塩基を示している。例えば、「１０２３５Ｔ→Ｃ」は、１０２３５番目のチミンがシトシンに変異したことを示している。また上記▲２▼の場合には、数字が塩基置換が行われた位置を示し、始めの英文字が置換前の塩基を後の英文字が置換後の塩基を示している。例えば、「Ｔ３３３６Ｃ」は、３３３６番目のチミンがシトシンに変異したことを示している。
【０００８】
また、塩基挿入については、例えば「７４６５ｉｎｓ−Ｃ」、或いは「７４６５Ｃ−ｉｎｓ」のように、挿入がなされた位置を数字で示した後に、挿入の意味を示す「ｉｎｓ」と、挿入された塩基とを記述して示す。塩基欠失については、例えば「２４８ｄｅｌ−Ａ」、或いは「２４８Ａｄｅｌ」のように、欠失がなされた位置を数字で示した後に、欠失の意味を示す「ｄｅｌ」と、欠失された塩基とを記述して示す。
また、アミノ酸置換については、タンパク質の種類と、２種類の英文字（アミノ酸の３文字表記）が数字を挟んだ記号とで示している。この場合に、英文字と数字の意味は、始めの英文字が置換前のアミノ酸を示し、後ろの英文字が置換後のアミノ酸を示している。また、数字は、対象となるタンパク質において、アミノ酸置換が行われた位置を示している。例えば、「Ｃｙｔｂ，Ｌｅｕ２３７Ｐｈｅ」は、Ｃｙｔｂにおいて、２３７番目のロイシンがフェニルアラニンに置換した変異であることを意味している。
【０００９】
また、「ｈｖｒ」は、高頻度変異部位（ｈｙｐｅｒｖａｒｉａｂｌｅｒｅｇｉｏｎ）を意味しており、ｈｖｒ１（３０３−３１７）及びｈｖｒ２（１６１８０−１６１９５）の２ヶ所がある。また、「Ｗ」は、野生型塩基配列（Ｗｉｌｄ−ｔｙｐｅｓｅｑｕｅｎｃｅ）を意味しており、標準となる改訂版ケンブリッジリファレンスシークエンス（ｒＣＲＳ，ｒｅｖｉｓｅｄＣａｍｂｒｉｄｇｅｒｅｆｅｒｅｎｃｅｓｅｑｕｅｎｃｅ；ＡｎｄｒｅｗｓＲ．Ｍ．，ＫｕｂａｃｋａＩ．，ＣｈｉｎｎｅｒｙＰ．Ｆ．，ＬｉｇｈｔｏｗｌｅｒｓＲ．Ｎ．，ＴｕｒｎｂｕｌｌＤ．Ｍ．，ＨｏｗｅｌｌＮ．ＲｅａｎａｌｙｓｉｓａｎｄｒｅｖｉｓｉｏｎｏｆｔｈｅＣａｍｂｒｉｄｇｅｒｅｆｅｒｅｎｃｅｓｅｑｕｅｎｃｅｆｏｒｈｕｍａｎｍｉｔｏｃｈｏｎｄｒｉａｌＤＮＡ．ＮａｔＧｅｎｅｔ１９９９；２３：１４７．）と同じ配列を意味している。「Ｗ」を付した位置として、高頻度変異部位１（ｈｖｒ１−３０３−３１７）を「Ｗ３０３−３１７ｈｖｒ１」、ＣＡリピート（ＣＡ−５１４−５２３）を「Ｗ５１４ｉｎｓＣＡ２」または「Ｗ５１４ｄｅｌＣＡ２」、Ｃストレッチ１（Ｃ１−５６８−５７３）を「Ｗ５６８Ｃｎ−ｉｎｓ」、１２ＳｒＲＮＡ（９５６−９６５）を「Ｗ９５６Ｃｎ−ｉｎｓ」、Ｃストレッチ２（Ｃ２−５８９５−５８９９）を「Ｗ５８９５Ｃｎ−ｉｎｓ」、９ｂｐ欠失／挿入（９−ｂｐｄｅｌ／ｉｎｓ−８２７２−８２８９）を「Ｗ８２７２−ｄｅｌ」、高頻度変異部位２（ｈｖｒ２−１６１８０−１６１９５）を「Ｗ１６１８０−９５−ｈｖｒ２」ということがある。これらの部位は、ｒＣＲＳと各個人との間に（或いは、各個人間においても）高度に変異が認められる。
【００１０】
遺伝子変異を検出する方法としては、当業者にとって公知の方法、例えばＤＮＡシークエンス、多重ＡＰＬＰ法、ＤＮＡマイクロアレイ等を使用したハブリダイゼーション法、Ｉｎｖａｄｅｒ法、Ｔａｑｍａｎプローブ法、Ｍａｓｓｃｏｄｅタグ法、対立遺伝子特異的ＰＣＲ法、ＲＦＬＰ法、多様固相蛍光ミニシークエンス法、免疫化シークエンス特異的オリゴヌクレオチドプローブアッセイ法などを例示することができるが、これらの方法に限定されることなく、将来的に開発される各種のＤＮＡ解析法を用いることが出来る。
第１の発明によれば、ヒトミトコンドリアＤＮＡの変異に基づいて、個人識別を行うことができる。
【００１１】
第２の発明は、ヒトミトコンドリアＤＮＡにおいて、４２ｉｎｓ−Ｃ，Ｃ６４Ｔ，Ｇ６８Ａ，Ａ７３Ｇ，Ｔ１３１Ｃ，Ｔ１４６Ｃ，Ｃ１５０Ｔ，Ｔ１５２Ｃ，Ａ１５３Ｇ，Ａ１８３Ｇ，Ｇ１８５Ａ，Ａ１８９Ｇ，１９０ｉｎｓ−Ａ，Ａ１９３Ｇ，Ｃ１９４Ｔ，Ｔ１９５Ｃ，Ｔ１９６Ｃ，Ｃ１９８Ｔ，Ｔ１９９Ｃ，Ａ２００Ｇ，Ａ２０２Ｇ，Ｇ２０３Ａ，Ｔ２０４Ｃ，Ｇ２０７Ａ，Ａ２１１Ｇ，Ａ２１４Ｇ，Ｇ２２８Ａ，Ａ２３５Ｇ，２４８ｄｅｌ−Ａ，Ｔ２５２Ｃ，Ｇ２６０Ａ，Ａ２６３Ｇ，Ｔ２７９Ｃ，Ａ２８４Ｇ，Ｃ２９８Ｔ，Ｃ３２５Ｔ，Ｃ３４８Ｇ，Ｔ４０８Ｇ，Ｔ４０８Ａ，Ｃ４３１Ｔ，Ｃ４４１Ｔ，４５１ｉｎｓ−Ｔ，Ｃ４５６Ｔ，Ｔ４８９Ｃ，Ｇ４９９Ａ，Ｔ５０４Ｃ，Ｇ５１３Ａ，Ｃ５３０Ｔ，５４０ｉｎｓ−Ｃ，Ｃ５５２Ｔ，Ａ６６３Ｇ，Ｔ６８１Ｃ，Ｇ７０９Ａ，Ｃ７５２Ｔ，Ａ８２７Ｇ，Ｔ９６１Ｃ，Ｃ９８４Ｔ，Ａ１０４１Ｇ，Ｃ１０４８Ｔ，Ｔ１１０７Ｃ，Ａ１１１８Ｇ，Ｔ１１１９Ｃ，Ａ１１４８Ｇ，Ｇ１２１１Ａ，Ｃ１３１０Ｔ，Ａ１３８２Ｃ，Ａ１４３８Ｇ，Ｇ１４４２Ａ，Ｇ１５９８Ａ，Ｇ１６６４Ａ，Ｇ１７０９Ａ，Ｇ１７１９Ａ，Ａ１７３６Ｇ，Ｔ１８１９Ｃ，Ｔ１８２２Ｃ，Ｇ１８８８Ａ，Ｔ１９７７Ｃ，２１５０ｉｎｓ−Ａ，Ａ２１７８Ｇ，Ａ２２２０Ｇ，Ａ２２４６Ｇ，Ｃ２２６３Ａ，Ｔ２３３０Ｃ，Ｔ２４１６Ｃ，Ｔ２６２６Ｃ，Ａ２７０６Ｇ，Ｃ２７６６Ｔ，Ｃ２７７２Ｔ，Ｇ２８３１Ａ，Ｃ２８３５Ｔ，Ｔ２８６３Ｃ，Ｇ３０１０Ａ，３１０６ｄｅｌ−Ｃ，３１０７ｄｅｌ−Ｃ，Ａ３１４５Ｇ，Ｃ３２０４Ｔ，Ｃ３２０６Ｔ，Ａ３２２１Ｇ，Ｔ３２７８Ｃ，Ｇ３３１６Ａ，Ａ３３２７Ｇ，Ｔ３３３６Ｃ，Ｇ３３９１Ａ，Ｔ３３９４Ｃ，Ａ３３９７Ｇ，Ｔ３４２３Ｃ，Ｃ３４４２Ｔ，Ｇ３４９６Ｔ，Ｃ３４９７Ｔ，Ａ３５３７Ｇ，Ｔ３５５２Ｃ，Ｔ３６４４Ｃ，Ａ３７２０Ｇ，Ａ３７５９Ｇ，Ａ３８７３Ｇ，Ｃ３９６０Ｔ，Ｃ３９７０Ｔ，Ｔ４０４７Ｃ，Ｇ４０４８Ａ，Ｃ４０７１Ｔ，Ｃ４０８６Ｔ，Ｇ４０９２Ａ，Ｇ４１１３Ａ，Ｔ４１１７Ｃ，Ａ４１３１Ｇ，Ａ４１６４Ｇ，Ａ４２０３Ｇ，Ｔ４２０９Ｃ，Ｔ４２３２Ｃ，Ｔ４２４８Ｃ，Ｃ４２５１Ｔ，Ａ４３４３Ｇ，Ｔ４３８６Ｃ，Ｃ４３９４Ｔ，Ｇ４４９１Ａ，Ｃ４５０５Ｔ，Ｇ４５４１Ｔ，Ｇ４６５５Ａ，Ｃ４６７０Ｔ，Ａ４７１５Ｇ，Ａ４７３２Ｇ，Ｔ４７３６Ｃ，Ｔ４７４２Ｃ，Ａ４７６９Ｇ，Ａ４７９３Ｇ，Ｇ４８２０Ａ，Ａ４８２４Ｇ，Ａ４８３３Ｇ，Ｔ４８５９Ｃ，Ｃ４８８３Ｔ，Ａ４８９５Ｇ，Ｇ４９２４Ａ，Ｃ４９２６Ｔ，Ａ４９５８Ｇ，Ｔ５０４８Ｃ，Ｃ５０４９Ｔ，Ｇ５０５４Ａ，Ｔ５１０８Ｃ，Ａ５１２８Ｇ，Ｇ５１４７Ａ，Ａ５１５３Ｇ，Ｃ５１７８Ａ，Ｔ５２０１Ｃ，Ｇ５２３１Ａ，Ｇ５２３７Ａ，Ａ５２４０Ｇ，Ｇ５２６１Ａ，Ｃ５２６３Ｔ，Ａ５３０１Ｇ，Ａ５３５１Ｇ，Ａ５３５１Ｃ，Ｇ５４１７Ａ，Ａ５４４１Ｇ，Ｇ５４６０Ａ，Ｔ５４６５Ｃ，Ｇ５４７１Ａ，Ｃ５６０１Ｔ，Ｔ５６５５Ｃ，Ｇ５７７３Ａ，Ｇ５８２１Ａ，Ｔ５８２６Ｃ，Ｔ５８２６Ｃ，Ａ５８９４Ｇ，Ａ５９００Ｃ，Ａ５９５１Ｇ，Ｇ６０１８Ａ，Ｇ６０２３Ａ，Ｇ６０２６Ａ，Ａ６０３９Ｇ，Ｇ６１７９Ａ，Ｔ６１８５Ｃ，Ｔ６２２１Ｃ，Ｔ６２５３Ｃ，Ｔ６２７８Ｃ，Ｇ６３０５Ａ，Ｔ６３９２Ｃ，Ｃ６４１０Ｔ，Ｔ６４１３Ｃ，Ｃ６４５５Ｔ，Ａ６５３３Ｇ，Ａ６５７５Ｇ，Ｔ６６１４Ｃ，Ｔ６６２０Ｃ，Ｃ６６４４Ｔ，Ｔ６６７１Ｃ，Ｔ６６８０Ｃ，Ｃ６６８９Ｔ，Ｔ６７１９Ｃ，Ａ６７３７Ｇ，Ａ６７５２Ｇ，Ｃ６７６１Ｔ，Ｇ６８９９Ａ，Ｇ６９６２Ａ，Ｃ６９８３Ｔ，Ｃ７０２８Ｔ，Ｔ７０５８Ｃ，Ｔ７１４２Ｃ，Ｃ７１９６Ａ，Ｃ７２１４Ｔ，Ｔ７２２０Ｃ，Ｃ７２３２Ｔ，Ｃ７２３５Ｔ，Ｃ７２５６Ｔ，Ｔ７２５８Ｃ，Ａ７４０３Ｇ，７５０２ｄｅｌ−Ｃ，Ｇ７５２１Ａ，Ｇ７６００Ａ，Ａ７６７３Ｇ，Ｔ７６８４Ｃ，Ｃ７７７４Ｔ，Ａ７８２２Ｇ，Ｇ７８５３Ａ，Ｔ７８６１Ｃ，Ｃ７８６７Ｔ，Ｃ７９０９Ｔ，Ｇ７９１２Ａ，Ｃ７９２７Ｔ，Ｇ８０２０Ａ，Ｔ８０６３Ｃ，Ａ８０７１Ｇ，Ａ８１４９Ｇ，Ｔ８１６７Ａ，Ａ８１８８Ｇ，Ｔ８２００Ｃ，Ｇ８２０６Ａ，Ａ８２２５Ｇ，Ｔ８２２７Ｃ，Ｇ８２５１Ａ，Ｃ８２９７Ｇ，Ａ８３０８Ｇ，Ｔ８３８３Ｃ，Ｃ８４１４Ｔ，Ｔ８４１９Ｃ，Ｃ８４２９Ａ，Ｔ８４５０Ｃ，Ａ８４７０Ｇ，Ｔ８４７３Ｃ，Ａ８５３７Ｇ，Ａ８５３７Ｇ，Ａ８５６３Ｇ，Ａ８５６３Ｇ，Ｇ８５７２Ａ，Ｇ８５８４Ａ，Ｃ８５９５Ｔ，Ｔ８６１０Ｃ，Ａ８６６４Ｇ，Ｃ８６８４Ｔ，Ａ８７０１Ｇ，Ｔ８７６２Ｃ，Ｃ８７９４Ｔ，Ｃ８８２９Ｔ，Ｇ８８５４Ａ，Ａ８８６０Ｇ，Ａ８８９４Ｔ，Ｃ８９０５Ａ，Ａ８９２９Ｇ，Ｃ８９６４Ｔ，Ｇ８９９４Ａ，Ａ９０４１Ｇ，Ｇ９０５３Ａ，Ｔ９０９０Ｃ，Ａ９１１５Ｇ，Ｇ９１２３Ａ，Ｔ９１２８Ｃ，Ｔ９１６５Ｃ，Ｔ９１７４Ｃ，Ａ９１８０Ｇ，Ａ９２４２Ｇ，Ａ９２８８Ｇ，Ｃ９２９６Ｔ，Ｇ９３０５Ａ，Ａ９３７７Ｇ，Ｔ９３８６Ｃ，Ｃ９４３１Ｔ，Ｇ９４７７Ａ，Ａ９４９４Ｇ，Ｔ９５４０Ｃ，Ｇ９５４８Ａ，Ｇ９５７５Ａ，Ｇ９６１２Ａ，Ａ９６６７Ｇ，Ｇ９７５５Ａ，Ｔ９８２４Ｃ，Ｔ９８２４Ａ，Ｔ９８３３Ｃ，Ｔ９８３６Ｇ，Ｇ９９２１Ａ，Ｇ９９３２Ａ，Ｔ９９３８Ｃ，Ｔ９９５０Ｃ，Ｔ９９５９Ｃ，Ｔ９９７７Ｃ，Ｔ１００８４Ｃ，Ｃ１０１０４Ｔ，Ｃ１０１８１Ｔ，Ｔ１０２３８Ｃ，Ｇ１０３１０Ａ，Ｔ１０３４５Ｃ，Ｇ１０３７３Ａ，Ａ１０３９７Ｇ，Ａ１０３９８Ｇ，Ｃ１０４００Ｔ，Ｔ１０４１０Ｃ，Ａ１０４１１Ｇ，Ｔ１０６０９Ｃ，Ｃ１０６３７Ｔ，Ｇ１０６４６Ａ，Ａ１０７５０Ｇ，Ｔ１０７９０Ｃ，Ｇ１０８０１Ａ，Ｔ１０８７３Ｃ，Ｔ１０９１５Ｃ，Ｃ１０９５４Ｔ，Ｃ１０９７６Ｔ，Ｇ１１０１６Ａ，Ｔ１１０１７Ｃ，Ａ１１０２０Ｇ，Ａ１１０８４Ｇ，Ｔ１１０８７Ｃ，Ａ１１１６７Ｇ，Ｃ１１２１５Ｔ，Ａ１１５３０Ｇ，Ｃ１１５３６Ｔ，Ｃ１１６４７Ｔ，Ｔ１１７０１Ｃ，Ｇ１１７１９Ａ，Ｔ１１８５４Ｃ，Ｇ１１９１４Ａ，Ｔ１１９４４Ｃ，Ａ１１９５９Ｇ，Ｇ１２００７Ａ，Ａ１２０２６Ｇ，Ａ１２０３０Ｇ，Ｃ１２０８４Ｔ，Ｃ１２０８８Ｔ，Ｃ１２０９２Ａ，Ａ１２２１０Ｇ，Ｔ１２３１１Ｃ，Ａ１２３５８Ｇ，Ａ１２３６１Ｇ，Ｇ１２３７２Ａ，Ｔ１２３９６Ｃ，Ａ１２３９７Ｇ，Ｃ１２４０５Ｔ，Ｇ１２４０６Ａ，Ｔ１２４６８Ｃ，Ｃ１２６３３Ｔ，Ｇ１２６５１Ｃ，Ｃ１２７０５Ｔ，Ｇ１２７７１Ａ，Ｔ１２８１１Ｃ，Ｃ１２８１６Ｔ，Ｔ１２８８０Ｃ，Ｃ１２８８２Ｔ，Ａ１３０５０Ｇ，Ｃ１３０５３Ｇ，Ａ１３１０４Ｇ，Ａ１３１０５Ｇ，Ｃ１３１１０Ｔ，Ｇ１３１３５Ａ，Ｔ１３１４３Ｃ，Ｔ１３２２４Ｃ，Ａ１３２７８Ｇ，Ｔ１３２８１Ｃ，Ｃ１３３３８Ｔ，Ｇ１３３５９Ａ，Ａ１３３９５Ｇ，Ａ１３４３４Ｇ，Ｔ１３５００Ｃ，Ａ１３５６３Ｇ，Ｇ１３５９０Ａ，Ａ１３６２９Ｇ，Ａ１３６５１Ｇ，Ｇ１３７０８Ａ，Ｇ１３７５９Ａ，Ｔ１３７６８Ｃ，Ａ１３８２７Ｇ，Ｔ１３８７９Ｃ，Ｇ１３９２８Ｃ，Ｇ１３９２８Ａ，Ａ１４００２Ｇ，Ｇ１４０１６Ａ，Ｃ１４０８２Ｔ，Ａ１４０９１Ｇ，Ａ１４１３３Ｇ，Ａ１４１６１Ｇ，Ｇ１４１６２Ａ，Ｔ１４１８０Ｃ，Ａ１４１８５Ｔ，Ｇ１４１９８Ａ，Ｔ１４２００Ｃ，Ｇ１４２２６Ａ，Ｃ１４２８１Ｔ，Ｔ１４２８７Ｃ，Ｔ１４３０８Ｃ，Ｔ１４３２５Ｃ，Ｇ１４３６４Ａ，Ｃ１４３６５Ｇ，Ｔ１４３７１Ｃ，Ｔ１４３８６Ｃ，Ｃ１４３８９Ｔ，Ａ１４４１７Ｇ，Ｔ１４４７０Ｃ，Ｇ１４４７６Ａ，Ａ１４５４８Ｇ，Ｃ１４５６２Ｇ，Ｇ１４５６９Ａ，Ａ１４５８２Ｇ，Ａ１４６０５Ｇ，Ｃ１４６６８Ｔ，Ａ１４６９３Ｇ，Ａ１４６９６Ｇ，Ａ１４７５０Ｇ，Ｃ１４７６６Ｔ，Ｔ１４７８３Ｃ，Ｃ１４９４４Ｔ，Ｔ１４９７９Ｃ，Ｇ１５０４３Ａ，Ｔ１５０６７Ｃ，Ｇ１５１４８Ａ，Ａ１５２１８Ｇ，Ｃ１５２２３Ｔ，Ａ１５２３６Ｇ，Ｇ１５３０１Ａ，Ｇ１５３１４Ａ，Ｇ１５３２３Ａ，Ａ１５３２６Ｇ，Ｃ１５３３１Ａ，Ｇ１５３４６Ａ，Ｇ１５３５５Ａ，Ｔ１５４４０Ｃ，Ｔ１５４７９Ｃ，Ａ１５４８７Ｔ，Ｇ１５４９７Ａ，Ｃ１５５０８Ｔ，Ｃ１５５１８Ｔ，Ａ１５５２４Ｇ，Ｃ１５５３５Ｔ，Ａ１５６６２Ｇ，Ｔ１５６７０Ｃ，Ａ１５７２４Ｇ，Ａ１５７５８Ｇ，Ｔ１５７８４Ｃ，Ｔ１５８５０Ｃ，Ａ１５８５１Ｇ，Ａ１５８６０Ｇ，Ａ１５８７４Ｇ，Ａ１５９２４Ｇ，Ｇ１５９２７Ａ，Ｔ１５９４１Ｃ，Ａ１５９５１Ｇ，Ａ１５９５４Ｇ，Ｇ１６０００Ａ，Ａ１６０５１Ｇ，Ｔ１６０７５Ｃ，Ｔ１６０９２Ｃ，Ｔ１６０９３Ｃ，Ｔ１６０９４Ｃ，Ｃ１６１１１Ｔ，Ｔ１６１２６Ｃ，Ｇ１６１２９Ａ，Ｔ１６１３６Ｃ，Ｔ１６１４０Ｃ，Ｇ１６１４５Ａ，Ｔ１６１５４Ｃ，Ａ１６１６２Ｇ，Ａ１６１６４Ｇ，Ｃ１６１６８Ｔ，Ｔ１６１７２Ｃ，Ｃ１６１７３Ｔ，Ｃ１６１７４Ｔ，Ｃ１６１７６Ｔ，Ａ１６１８３Ｃ，Ｔ１６１８９Ｃ，Ｔ１６２０９Ｃ，Ｃ１６２１４Ｇ，Ａ１６２１６Ｇ，Ｔ１６２１７Ｃ，Ｃ１６２２３Ｔ，Ａ１６２２７Ｇ，Ｃ１６２３２Ａ，Ｃ１６２３４Ｔ，Ａ１６２３５Ｇ，Ｔ１６２４３Ｃ，Ｇ１６２４４Ａ，Ｃ１６２４５Ｔ，Ｔ１６２４９Ｃ，Ａ１６２５２Ｃ，Ａ１６２５４Ｇ，Ｃ１６２５６Ｔ，Ｃ１６２５７Ａ，Ａ１６２５８Ｔ，１６２５８ｉｎｓ−Ｃ，Ｃ１６２６０Ｔ，Ｃ１６２６１Ｔ，Ｔ１６２６３Ｃ，Ａ１６２６５Ｇ，Ｃ１６２６６Ｔ，Ｃ１６２６８Ｔ，Ｇ１６２７４Ａ，Ｃ１６２７８Ｔ，Ａ１６２８４Ｇ，Ｃ１６２８７Ｔ，Ｔ１６２８８Ｃ，Ｃ１６２９０Ｔ，Ｃ１６２９１Ｔ，Ｃ１６２９４Ｔ，Ｃ１６２９５Ｔ，Ｔ１６２９７Ｃ，Ｔ１６２９８Ｃ，１６２９８ｉｎｓ−Ａ，Ａ１６２９９Ｇ，Ａ１６３００Ｇ，Ｔ１６３０４Ｃ，Ａ１６３０９Ｇ，Ｔ１６３１１Ｃ，Ａ１６３１６Ｇ，Ａ１６３１７Ｇ，Ｇ１６３１９Ａ，Ｔ１６３２４Ｃ，Ｔ１６３２５Ｃ，Ｔ１６３４２Ｃ，Ｃ１６３４４Ｔ，Ｔ１６３５６Ｃ，Ｔ１６３５７Ｃ，Ｔ１６３６２Ｃ，Ａ１６３６７Ｃ，Ｔ１６３６８Ｃ，Ｇ１６３７３Ａ，Ｔ１６３８１Ｃ，Ｇ１６３９０Ａ，Ａ１６３９９Ｇ，Ｃ１６４００Ｔ，Ａ１６４６３Ｇ，Ａ１６４９７Ｇ，Ｔ１６５１９Ｃのうちの少なくとも一つ、または二つ以上の塩基の変異に基づいて、その者がパーキンソン病となるか否かについての判断資料を与えることを特徴とするヒトミトコンドリア遺伝子変異に基づく遺伝子検出法である。
【００１２】
パーキンソン病患者群においては、５５７個の変異が確認された。第２の発明では、これら５５７ヶ所の変異のいずれか（一つ、または二つ以上）を検出することにより、その者がパーキンソン病となるか否かを判断するための資料を与えることができる。
なお、第２の発明において、好ましくは、Ｔ１３１Ｃ，Ｔ１４６Ｃ，Ｃ１５０Ｔ，Ａ１５３Ｇ，Ａ１８９Ｇ，Ｔ１９５Ｃ，Ｇ２０７Ａ，Ａ２１４Ｇ，Ｃ２９８Ｔ，Ｃ４３１Ｔ，Ｇ７０９Ａ，Ａ８２７Ｇ，Ｔ１１１９Ｃ，Ａ１４３８Ｇ，Ｇ１７１９Ａ，Ｇ１８８８Ａ，Ｔ２６２６Ｃ，Ｃ２７７２Ｔ，Ｔ３３９４Ｃ，Ｃ３４９７Ｔ，Ｔ４３８６Ｃ，Ａ４７１５Ｇ，Ａ４７３２Ｇ，Ａ４７９３Ｇ，Ａ４８３３Ｇ，Ｔ４８５９Ｃ，Ａ４８９５Ｇ，Ａ４９５８Ｇ，Ｃ５０４９Ｔ，Ｔ５１０８Ｃ，Ｇ５１４７Ａ，Ｇ５２３１Ａ，Ｇ５４１７Ａ，Ｔ５４６５Ｃ，Ｇ５７７３Ａ，Ｔ６１８５Ｃ，Ｔ６２５３Ｃ，Ｃ６４１０Ｔ，Ｃ６６８９Ｔ，Ａ６７５２Ｇ，Ｃ７０２８Ｔ，Ｃ７１９６Ａ，Ｃ７８６７Ｔ，Ｔ８２００Ｃ，Ａ８７０１Ｇ，Ｔ９０９０Ｃ，Ｇ９１２３Ａ，Ｔ９５４０Ｃ，Ｃ１０１８１Ｔ，Ｇ１０３７３Ａ，Ｃ１０４００Ｔ，Ｔ１０８７３Ｃ，Ｃ１０９７６Ｔ，Ｔ１１０１７Ｃ，Ａ１１０８４Ｇ，Ｃ１１２１５Ｔ，Ｇ１１７１９Ａ，Ｇ１１９１４Ａ，Ａ１２３５８Ｇ，Ｇ１２３７２Ａ，Ｃ１２７０５Ｔ，Ｇ１２７７１Ａ，Ｔ１２８８０Ｃ，Ａ１３１０４Ｇ，Ｇ１４３６４Ａ，Ｔ１４３７１Ｃ，Ｇ１４４７６Ａ，Ｇ１４５６９Ａ，Ｔ１４７８３Ｃ，Ｇ１５０４３Ａ，Ｔ１５０６７Ｃ，Ｇ１５３０１Ａ，Ｇ１５３２３Ａ，Ｔ１５４４０Ｃ，Ａ１５４８７Ｔ，Ｇ１５４９７Ａ，Ｃ１５５３５Ｔ，Ｔ１５７８４Ｃ，Ｔ１５８５０Ｃ，Ａ１５８６０Ｇ，Ａ１５８７４Ｇ，Ｔ１５９４１Ｃ，Ａ１５９５１Ｇ，Ａ１５９５４Ｇ，Ｔ１６０９２Ｃ，Ｃ１６１１１Ｔ，Ｔ１６１２６Ｃ，Ｔ１６２０９Ｃ，Ｔ１６２１７Ｃ，Ｃ１６２２３Ｔ，Ｃ１６２３２Ａ，Ｃ１６２３４Ｔ，Ｇ１６２４４Ａ，Ｃ１６２５７Ａ，Ｃ１６２６０Ｔ，Ｃ１６２６１Ｔ，Ｇ１６２７４Ａ，Ｃ１６２８７Ｔ，Ｃ１６２９１Ｔ，Ｔ１６２９８Ｃ，Ｔ１６３２４Ｃ，Ｔ１６３２５Ｃ，Ａ１６４６３Ｇ，Ａ１６４９７Ｇのうちの少なくとも一つ、または二つ以上の塩基の変異に基づくことができる。
本発明者らの解析によれば、百寿者に比べてパーキンソン病患者に多く確認された１０４ヶ所の変異（百寿者及びパーキンソン病患者のいずれにも変異が認められ、かつパーキンソン病患者により多くの数が認められた変異）の有無を確認することにより、その者がパーキンソン病患者となる可能性が高いか否かについての判断資料を与えることができる。
【００１３】
また、第２の発明において、好ましくは、４２ｉｎｓ−Ｃ，Ａ１８３Ｇ，Ｇ１８５Ａ，Ａ１９３Ｇ，Ｔ１９６Ｃ，Ｃ１９８Ｔ，Ｇ２０３Ａ，Ａ２１１Ｇ，Ｇ２２８Ａ，Ｔ２５２Ｃ，Ｔ２７９Ｃ，Ａ２８４Ｇ，Ｃ３２５Ｔ，Ｃ３４８Ｇ，Ｔ４０８Ｇ，Ｃ４４１Ｔ，４５１ｉｎｓ−Ｔ，Ｔ５０４Ｃ，Ｇ５１３Ａ，Ｃ５３０Ｔ，５４０ｉｎｓ−Ｃ，Ｃ５５２Ｔ，Ｔ９６１Ｃ，Ｃ９８４Ｔ，Ａ１０４１Ｇ，Ａ１１１８Ｇ，Ｇ１２１１Ａ，Ｇ１６６４Ａ，Ｇ１７０９Ａ，Ｔ１８１９Ｃ，Ｔ１８２２Ｃ，Ａ２１７８Ｇ，Ａ２２２０Ｇ，Ｃ２２６３Ａ，Ｔ２３３０Ｃ，Ｔ２４１６Ｃ，Ｃ２８３５Ｔ，Ｔ２８６３Ｃ，３１０７ｄｅｌ−Ｃ，Ａ３１４５Ｇ，Ｃ３２０４Ｔ，Ａ３２２１Ｇ，Ａ３３２７Ｇ，Ｔ３３３６Ｃ，Ａ３３９７Ｇ，Ｔ３４２３Ｃ，Ｃ３４４２Ｔ，Ｔ３５５２Ｃ，Ｔ３６４４Ｃ，Ａ３７２０Ｇ，Ａ３８７３Ｇ，Ｃ３９６０Ｔ，Ｔ４０４７Ｃ，Ｇ４０９２Ａ，Ｇ４１１３Ａ，Ａ４１３１Ｇ，Ａ４２０３Ｇ，Ｔ４２３２Ｃ，Ｃ４２５１Ｔ，Ｇ４４９１Ａ，Ｇ４５４１Ｔ，Ｃ４６７０Ｔ，Ｔ４７３６Ｃ，Ｔ４７４２Ｃ，Ｇ４９２４Ａ，Ｃ４９２６Ｔ，Ｔ５０４８Ｃ，Ｇ５０５４Ａ，Ａ５１２８Ｇ，Ｔ５２０１Ｃ，Ｇ５２３７Ａ，Ａ５２４０Ｇ，Ｇ５２６１Ａ，Ｃ５２６３Ｔ，Ａ５３５１Ｃ，Ａ５４４１Ｇ，Ｇ５４７１Ａ，Ｔ５６５５Ｃ，Ｇ５８２１Ａ，Ｔ５８２６Ｃ，Ｔ５８２６Ｃ，Ａ５９００Ｃ，Ａ５９５１Ｇ，Ｇ６０２６Ａ，Ａ６０３９Ｇ，Ｇ６１７９Ａ，Ｔ６２７８Ｃ，Ｇ６３０５Ａ，Ａ６５３３Ｇ，Ａ６５７５Ｇ，Ｔ６６１４Ｃ，Ｃ６６４４Ｔ，Ｔ６６７１Ｃ，Ｔ６７１９Ｃ，Ｃ６７６１Ｔ，Ｇ６８９９Ａ，Ｃ６９８３Ｔ，Ｔ７０５８Ｃ，Ｔ７１４２Ｃ，Ｃ７２１４Ｔ，Ｔ７２２０Ｃ，Ｃ７２３５Ｔ，Ｔ７２５８Ｃ，７５０２ｄｅｌ−Ｃ，Ａ７６７３Ｇ，Ｃ７７７４Ｔ，Ｔ７８６１Ｃ，Ｃ７９０９Ｔ，Ｃ７９２７Ｔ，Ｔ８０６３Ｃ，Ａ８１４９Ｇ，Ｔ８１６７Ａ，Ａ８１８８Ｇ，Ａ８２２５Ｇ，Ｔ８２２７Ｃ，Ｃ８２９７Ｇ，Ａ８３０８Ｇ，Ｔ８３８３Ｃ，Ｔ８４１９Ｃ，Ｃ８４２９Ａ，Ａ８４７０Ｇ，Ａ８５３７Ｇ，Ａ８５３７Ｇ，Ｇ８５７２Ａ，Ｃ８５９５Ｔ，Ｔ８６１０Ｃ，Ａ８６６４Ｇ，Ｃ８６８４Ｔ，Ｇ８８５４Ａ，Ａ８８９４Ｔ，Ｃ８９０５Ａ，Ａ８９２９Ｇ，Ａ９０４１Ｇ，Ａ９１１５Ｇ，Ｔ９１７４Ｃ，Ａ９２４２Ｇ，Ａ９２８８Ｇ，Ｇ９３０５Ａ，Ｔ９３８６Ｃ，Ｃ９４３１Ｔ，Ｇ９４７７Ａ，Ｇ９６１２Ａ，Ｔ９８３３Ｃ，Ｔ９８３６Ｇ，Ｇ９９２１Ａ，Ｇ９９３２Ａ，Ｔ９９３８Ｃ，Ｔ９９５９Ｃ，Ｔ９９７７Ｃ，Ｔ１００８４Ｃ，Ｔ１０２３８Ｃ，Ａ１０４１１Ｇ，Ｃ１０６３７Ｔ，Ｇ１０６４６Ａ，Ａ１０７５０Ｇ，Ｔ１０７９０Ｃ，Ｔ１０９１５Ｃ，Ｃ１０９５４Ｔ，Ｇ１１０１６Ａ，Ａ１１０２０Ｇ，Ｔ１１０８７Ｃ，Ａ１１１６７Ｇ，Ａ１１５３０Ｇ，Ｔ１１７０１Ｃ，Ｔ１１８５４Ｃ，Ａ１１９５９Ｇ，Ａ１２０３０Ｇ，Ｃ１２０８４Ｔ，Ｃ１２０９２Ａ，Ａ１２２１０Ｇ，Ｔ１２３９６Ｃ，Ａ１２３９７Ｇ，Ｔ１２４６８Ｃ，Ｃ１２６３３Ｔ，Ｃ１２８１６Ｔ，Ａ１３０５０Ｇ，Ｃ１３０５３Ｇ，Ｔ１３１４３Ｃ，Ｔ１３２２４Ｃ，Ｔ１３２８１Ｃ，Ｃ１３３３８Ｔ，Ｇ１３３５９Ａ，Ａ１３３９５Ｇ，Ａ１３４３４Ｇ，Ｔ１３５００Ｃ，Ａ１３６２９Ｇ，Ｔ１３８７９Ｃ，Ｇ１４０１６Ａ，Ｃ１４０８２Ｔ，Ａ１４１６１Ｇ，Ｇ１４１６２Ａ，Ａ１４１８５Ｔ，Ｇ１４１９８Ａ，Ｇ１４２２６Ａ，Ｔ１４３０８Ｃ，Ｃ１４３６５Ｇ，Ｔ１４３８６Ｃ，Ｃ１４３８９Ｔ，Ａ１４４１７Ｇ，Ａ１４５４８Ｇ，Ｃ１４５６２Ｇ，Ａ１４５８２Ｇ，Ａ１４６９３Ｇ，Ａ１４６９６Ｇ，Ａ１４７５０Ｇ，Ｇ１５１４８Ａ，Ｇ１５３１４Ａ，Ｇ１５３５５Ａ，Ｔ１５４７９Ｃ，Ｔ１５６７０Ｃ，Ａ１５７５８Ｇ，Ｇ１６０００Ａ，Ｔ１６０７５Ｃ，Ｔ１６０９４Ｃ，Ｇ１６１４５Ａ，Ｔ１６１５４Ｃ，Ｃ１６１７３Ｔ，Ｃ１６１７４Ｔ，Ａ１６１８３Ｃ，Ｔ１６１８９Ｃ，Ｃ１６２１４Ｇ，Ａ１６２１６Ｇ，Ａ１６２３５Ｇ，Ａ１６２５２Ｃ，Ａ１６２５４Ｇ，Ｃ１６２５６Ｔ，Ａ１６２５８Ｔ，１６２５８ｉｎｓ−Ｃ，Ｔ１６２６３Ｃ，Ａ１６２６５Ｇ，Ｃ１６２６８Ｔ，Ｔ１６２８８Ｃ，１６２９８ｉｎｓ−Ａ，Ａ１６２９９Ｇ，Ａ１６３１６Ｇ，Ａ１６３１７Ｇ，Ｔ１６３４２Ｃ，Ａ１６３６７Ｃ，Ｔ１６３６８Ｃ，Ｇ１６３７３Ａ，Ｔ１６３８１Ｃ，Ａ１６３９９Ｇ，Ｃ１６４００Ｔのうちの少なくとも一つ、または二つ以上の塩基の変異に基づくことができる。
本発明者らの解析によれば、百寿者群には認められず、パーキンソン病患者にのみ確認された２４３ヶ所の変異の有無を確認することにより、その者がパーキンソン病患者となる可能性が高いか否かについての判断資料を与えることができる。
【００１４】
また、百寿者群においては、５１９個の変異が確認された。これらの変異のうち、百寿者群に多く見られた３３１ヶ所の変異のいずれか（一つ、または二つ以上）、またはパーキンソン病患者群には認められず百寿者群にのみ確認された２０５ヶ所の変異を検出することにより、その者が長寿者となるか否か（或いは、パーキンソン病となりにくいか否か）を判断するための資料を与えることができる（なお、３３１ヶ所のうちの１２６ヶ所については、パーキンソン病と百寿者のいずれにも確認された変異であって、百寿者に多く見られたものである）。
こうして、第３の発明は、ヒトミトコンドリアＤＮＡにおいて、Ｔ６３Ｃ，Ｃ６４Ｔ，６６ｄｅｌ−Ｇ，Ａ９３Ｇ，Ｇ９４Ａ，Ｇ１０３Ａ，Ｃ１５１Ｔ，１９０ｉｎｓ−Ａ，Ａ１９１Ｇ，Ｃ１９４Ｔ，Ｔ１９９Ｃ，Ａ２００Ｇ，Ｔ２０４Ｃ，Ａ２１０Ｇ，Ａ２３５Ｇ，Ａ２５７Ｇ，Ａ２６３Ｇ，Ｃ２８０Ｔ，Ａ２８１Ｇ，２８６ｄｅｌ−Ａ，２８７ｄｅｌ−Ａ，３１０ｉｎｓ−Ｃ，Ｃ３４８Ｔ，Ａ３５１Ｃ，Ａ３６８Ｇ，Ｇ３８０Ｃ，Ｃ３８２Ｇ，Ａ３８５Ｔ，Ｔ４０８Ａ，Ｃ４５６Ｔ，Ｃ４８１Ｔ，Ｇ４９９Ａ，Ｃ５０６Ｔ，Ａ５３３Ｇ，Ａ５４６Ｇ，Ａ６６３Ｇ，Ｔ６８１Ｃ，Ｃ７５２Ｔ，Ａ８５６Ｇ，Ｃ９８３Ｔ，Ａ９９８Ｇ，Ｃ１０４８Ｔ，Ｔ１１０７Ｃ，Ａ１３８２Ｃ，Ｔ１４２０Ｃ，Ｃ１７３４Ｔ，Ａ１７３６Ｇ，Ｔ１９７７Ｃ，２１５０ｉｎｓ−Ａ，Ａ２７０６Ｇ，Ｃ２７６６Ｔ，Ｔ２８８７Ｃ，Ｇ３０１０Ａ，３１０６ｄｅｌ−Ｃ，Ｃ３２０６Ｔ，Ｔ３３３８Ｃ，Ｇ３３９１Ａ，Ｔ３４５６Ｃ，Ｇ３４９６Ｔ，Ａ３５２０Ｇ，Ｔ３５５２Ａ，Ｇ３５９１Ａ，Ｃ３６９６Ｔ，Ａ３７６８Ｇ，Ｔ３８２６Ｃ，Ｇ３８８２Ａ，Ｃ３９６３Ａ，Ｃ３９７０Ｔ，Ｇ４０４８Ａ，Ｔ４０６２Ｃ，Ｃ４０７１Ｔ，Ｃ４０８６Ｔ，Ａ４１６４Ｇ，Ｔ４２４８Ｃ，Ａ４３１０Ｇ，Ｔ４６１２Ｃ，Ｇ４６５５Ａ，Ｇ４６５９Ａ，Ｔ４６８８Ｃ，Ｔ４７０５Ｃ，Ａ４８２４Ｇ，Ｃ４８５０Ｔ，Ｃ４８８３Ｔ，Ａ５１２７Ｇ，Ａ５１５３Ｇ，Ｃ５１７８Ａ，Ａ５３０１Ｇ，Ａ５３５１Ｇ，Ｃ５３７９Ｔ，Ｔ５４４２Ｃ，Ｇ５４６０Ａ，Ｔ５４９２Ｃ，Ａ５５３９Ｇ，Ｃ５６０１Ｔ，Ｔ５６２８Ｃ，Ｇ５７４４Ａ，Ｔ５７８８Ｃ，Ａ５８９４Ｇ，Ｔ５９６４Ｃ，Ｇ５９７９Ａ，Ｃ６０５３Ｔ，Ａ６１４６Ｇ，Ｃ６２４２Ｔ，Ｇ６２６１Ａ，Ａ６２９９Ｇ，Ａ６３３２Ｇ，Ｇ６３８３Ａ，Ｔ６３９２Ｃ，Ａ６４１６Ｇ，Ｃ６４５２Ｔ，Ｃ６４５５Ｔ，Ｃ６４８３Ｔ，Ｔ６５１２Ｃ，Ｔ６５２４Ｃ，Ｃ６５４２Ｔ，Ｃ６５６９Ａ，Ｔ６６４１Ｃ，Ｔ６６８０Ｃ，Ａ６６９８Ｇ，Ｇ６９６２Ａ，Ａ７１４６Ｇ，Ｔ７１９１Ｃ，Ｃ７２４４Ｔ，Ｔ７２７０Ｃ，Ａ７３５２Ｔ，Ｔ７３８９Ｃ，Ａ７４０３Ｇ，Ｃ７４９２Ｔ，Ｇ７５９８Ａ，Ｔ７６８４Ｃ，Ｔ７７３８Ｃ，Ａ７７５５Ｇ，Ｃ７８１０Ｔ，Ｇ７８５３Ａ，Ｃ７８６８Ｔ，Ｃ７８９１Ｔ，Ｔ７９６１Ｃ，Ｇ８０２０Ａ，Ａ８０２１Ｇ，Ａ８０７４Ｇ，Ｃ８１４０Ｔ，Ｔ８１６７Ｃ，Ｃ８２０３Ｔ，Ｇ８２５１Ａ，Ｔ８２６５Ｃ，Ｃ８２７０Ｔ，Ｇ８２９０Ａ，Ａ８２９１Ｇ，Ｇ８３９２Ａ，Ａ８４１３Ｇ，Ｃ８４１４Ｔ，Ｃ８４５５Ｔ，Ｃ８４６１Ｔ，Ｔ８４７３Ｃ，Ａ８４８９Ｇ，Ｇ８５５７Ａ，Ｇ８５５７Ａ，Ａ８５６３Ｇ，Ａ８５６３Ｇ，Ｔ８６５４Ｃ，Ａ８７８４Ｇ，Ｃ８７８８Ｔ，Ｃ８７９４Ｔ，Ａ８８１２Ｇ，Ｃ８８２９Ｔ，Ｃ８８４４Ｔ，Ｃ８９６４Ｔ，Ｔ９０１７Ｃ，Ａ９０６９Ｇ，Ｔ９０８４Ｃ，Ｃ９０９９Ａ，Ｃ９１２９Ｔ，Ｔ９１６５Ｃ，Ａ９１８０Ｇ，Ｃ９２９３Ｔ，Ｃ９２９６Ｔ，Ａ９２９９Ｇ，Ａ９３４１Ｔ，Ａ９３７７Ｇ，Ｔ９４７９Ｃ，Ｃ９５３６Ｔ，Ａ９５４５Ｇ，Ｇ９５４８Ａ，Ｔ９７５０Ｃ，Ｇ９７５５Ａ，Ｇ９８０４Ａ，Ｃ９８１２Ｔ，Ｔ９８２４Ａ，Ａ９８４３Ｇ，Ｔ９９５０Ｃ，Ｇ９９６２Ａ，Ｃ１０１０４Ｔ，Ｇ１０１７２Ａ，Ｔ１０２７４Ｃ，Ｇ１０３１０Ａ，Ｔ１０３４５Ｃ，Ａ１０３９７Ｇ，Ａ１０３９８Ｇ，Ｔ１０４１０Ｃ，Ｔ１０６０９Ｃ，Ｇ１０８０１Ａ，Ａ１０８７６Ｇ，Ａ１０９７２Ｇ，Ｃ１１０５９Ｔ，Ｔ１１１１３Ｃ，Ｃ１１１４６Ｔ，Ｇ１１１４９Ａ，Ｃ１１１５１Ｔ，Ｔ１１４３７Ｃ，Ｃ１１５３６Ｔ，Ｃ１１６４７Ｔ，Ｃ１１６６５Ｔ，Ｇ１１６９６Ａ，Ｔ１１７２２Ｃ，Ｔ１１７７０Ｃ，Ｔ１１９４４Ｃ，Ｇ１１９６９Ａ，Ｇ１２００７Ａ，Ａ１２０２６Ｇ，Ａ１２０４０Ｇ，Ｔ１２０９１Ｃ，Ｇ１２１９２Ａ，Ａ１２２３４Ｇ，Ｔ１２３５４Ｃ，Ａ１２３６１Ｇ，Ｃ１２４０５Ｔ，Ｇ１２４０６Ａ，Ｔ１２４０８Ｃ，Ｇ１２６２２Ａ，Ｇ１２６３０Ａ，Ａ１２６３４Ｇ，Ｇ１２６５１Ａ，Ｔ１２８０４Ｃ，Ｔ１２８１１Ｃ，Ａ１２８３４Ｇ，Ｃ１３０１１Ｔ，Ａ１３０５７Ｇ，Ｃ１３１１０Ｔ，Ｔ１３２１５Ｃ，Ａ１３２２１Ｇ，Ｇ１３２２５Ａ，Ｃ１３２５１Ｔ，Ａ１３２６３Ｇ，Ａ１３２６９Ｇ，Ｃ１３３８３Ｔ，Ａ１３４１３Ｇ，Ｔ１３４６１Ｃ，Ａ１３５６３Ｇ，Ｇ１３５９０Ａ，Ａ１３６０６Ｇ，Ａ１３６１４Ｇ，Ｔ１３６１７Ｃ，Ａ１３６５１Ｇ，Ｃ１３６９５Ａ，Ｇ１３７０８Ａ，Ｇ１３７５９Ａ，Ｇ１３８１０Ａ，Ａ１３８８７Ｇ，Ｇ１３９２８Ｃ，Ａ１４００１Ｇ，Ａ１４００２Ｇ，Ａ１４０５３Ｇ，Ａ１４１３３Ｇ，Ｃ１４１４９Ｔ，Ｃ１４１５８Ｔ，Ｔ１４１８０Ｃ，Ｔ１４２００Ｃ，Ｃ１４２８１Ｇ，Ｔ１４２８７Ｃ，Ｔ１４３１８Ｃ，Ｔ１４４７０Ｃ，Ｇ１４５４４Ａ，Ａ１４６０５Ｇ，Ｃ１４６６８Ｔ，Ｃ１４８６７Ｔ，Ｔ１４９７９Ｃ，Ｃ１５２２３Ｔ，Ａ１５２３５Ｇ，Ａ１５２３６Ｇ，Ｃ１５５０８Ｔ，Ａ１５５２４Ｇ，Ａ１５６６２Ｇ，Ａ１５７２４Ｇ，Ａ１５８５１Ｇ，Ｇ１５８８４Ａ，Ｇ１５９２７Ａ，１５９４０ｄｅｌ−Ｔ，Ａ１５９７４Ｇ，Ａ１６０３７Ｇ，Ａ１６０５１Ｇ，Ｔ１６０８６Ｃ，Ｔ１６０９３Ｃ，Ｇ１６１２９Ａ，Ｔ１６１４０Ｃ，Ａ１６１６２Ｇ，Ｃ１６１６９Ｔ，Ｃ１６１７６Ｔ，Ｃ１６２０１Ｔ，Ａ１６２１５Ｇ，Ｔ１６２２４Ｃ，Ａ１６２２７Ｇ，Ａ１６２４０Ｇ，Ｔ１６２４３Ｃ，Ｃ１６２５７Ｔ，Ｃ１６２６６Ａ，Ａ１６２６９Ｇ，Ｃ１６２７０Ｔ，Ｃ１６２７８Ｔ，Ｃ１６２９０Ｔ，Ｃ１６２９１Ｇ，Ｃ１６２９２Ｔ，Ｃ１６２９２Ｇ，Ｃ１６２９４Ｔ，Ｃ１６２９６Ｔ，Ｔ１６２９７Ｃ，Ａ１６３０２Ｇ，Ｔ１６３０４Ｃ，Ａ１６３０９Ｇ，Ａ１６３１８Ｔ，Ｇ１６３１９Ａ，Ｃ１６３２０Ｔ，Ｃ１６３２７Ｔ，Ｔ１６３５２Ｃ，Ｃ１６３５５Ｔ，Ｃ１６３６０Ｔ，Ｔ１６３６２Ｃ，Ｇ１６３９０Ａ，Ｇ１６４５６Ｃ，Ｔ１６５１９Ｃ，Ａ１６５２３Ｇ，Ｃ１６５２７Ｔのうちの少なくとも一つ、または二つ以上の塩基の変異に基づいて、その者が長寿者となるか否かについての判断資料を与えることを特徴とするヒトミトコンドリア遺伝子変異に基づく遺伝子検出法である。これら３３１ヶ所の変異は、パーキンソン病患者群に比べて、百寿者群に多く見られた変異である。
【００１５】
また、第４の発明は、第３の発明において、ヒトミトコンドリアＤＮＡにおいて、Ｔ６３Ｃ，６６ｄｅｌ−Ｇ，Ａ９３Ｇ，Ｇ９４Ａ，Ｇ１０３Ａ，Ｃ１５１Ｔ，Ａ１９１Ｇ，Ａ２１０Ｇ，Ａ２５７Ｇ，Ｃ２８０Ｔ，Ａ２８１Ｇ，２８６ｄｅｌ−Ａ，２８７ｄｅｌ−Ａ，３１０ｉｎｓ−Ｃ，Ｃ３４８Ｔ，Ａ３５１Ｃ，Ａ３６８Ｇ，Ｇ３８０Ｃ，Ｃ３８２Ｇ，Ａ３８５Ｔ，Ｃ４８１Ｔ，Ｃ５０６Ｔ，Ａ５３３Ｇ，Ａ５４６Ｇ，Ａ８５６Ｇ，Ｃ９８３Ｔ，Ａ９９８Ｇ，Ｔ１４２０Ｃ，Ｃ１７３４Ｔ，Ｔ２８８７Ｃ，Ｔ３３３８Ｃ，Ｔ３４５６Ｃ，Ａ３５２０Ｇ，Ｔ３５５２Ａ，Ｇ３５９１Ａ，Ｃ３６９６Ｔ，Ａ３７６８Ｇ，Ｔ３８２６Ｃ，Ｇ３８８２Ａ，Ｃ３９６３Ａ，Ｔ４０６２Ｃ，Ａ４３１０Ｇ，Ｔ４６１２Ｃ，Ｇ４６５９Ａ，Ｔ４６８８Ｃ，Ｔ４７０５Ｃ，Ｃ４８５０Ｔ，Ａ５１２７Ｇ，Ｃ５３７９Ｔ，Ｔ５４４２Ｃ，Ｔ５４９２Ｃ，Ａ５５３９Ｇ，Ｔ５６２８Ｃ，Ｇ５７４４Ａ，Ｔ５７８８Ｃ，Ｔ５９６４Ｃ，Ｇ５９７９Ａ，Ｃ６０５３Ｔ，Ａ６１４６Ｇ，Ｃ６２４２Ｔ，Ｇ６２６１Ａ，Ａ６２９９Ｇ，Ａ６３３２Ｇ，Ｇ６３８３Ａ，Ａ６４１６Ｇ，Ｃ６４５２Ｔ，Ｃ６４８３Ｔ，Ｔ６５１２Ｃ，Ｔ６５２４Ｃ，Ｃ６５４２Ｔ，Ｃ６５６９Ａ，Ｔ６６４１Ｃ，Ａ６６９８Ｇ，Ａ７１４６Ｇ，Ｔ７１９１Ｃ，Ｃ７２４４Ｔ，Ｔ７２７０Ｃ，Ａ７３５２Ｔ，Ｔ７３８９Ｃ，Ｃ７４９２Ｔ，Ｇ７５９８Ａ，Ｔ７７３８Ｃ，Ａ７７５５Ｇ，Ｃ７８１０Ｔ，Ｃ７８６８Ｔ，Ｃ７８９１Ｔ，Ｔ７９６１Ｃ，Ａ８０２１Ｇ，Ａ８０７４Ｇ，Ｃ８１４０Ｔ，Ｔ８１６７Ｃ，Ｃ８２０３Ｔ，Ｔ８２６５Ｃ，Ｃ８２７０Ｔ，Ｇ８２９０Ａ，Ａ８２９１Ｇ，Ｇ８３９２Ａ，Ａ８４１３Ｇ，Ｃ８４５５Ｔ，Ｃ８４６１Ｔ，Ａ８４８９Ｇ，Ｇ８５５７Ａ，Ｇ８５５７Ａ，Ｔ８６５４Ｃ，Ａ８７８４Ｇ，Ｃ８７８８Ｔ，Ａ８８１２Ｇ，Ｃ８８４４Ｔ，Ｔ９０１７Ｃ，Ａ９０６９Ｇ，Ｔ９０８４Ｃ，Ｃ９０９９Ａ，Ｃ９１２９Ｔ，Ｃ９２９３Ｔ，Ａ９２９９Ｇ，Ａ９３４１Ｔ，Ｔ９４７９Ｃ，Ｃ９５３６Ｔ，Ａ９５４５Ｇ，Ｔ９７５０Ｃ，Ｇ９８０４Ａ，Ｃ９８１２Ｔ，Ａ９８４３Ｇ，Ｇ９９６２Ａ，Ｇ１０１７２Ａ，Ｔ１０２７４Ｃ，Ａ１０８７６Ｇ，Ａ１０９７２Ｇ，Ｃ１１０５９Ｔ，Ｔ１１１１３Ｃ，Ｃ１１１４６Ｔ，Ｇ１１１４９Ａ，Ｃ１１１５１Ｔ，Ｔ１１４３７Ｃ，Ｃ１１６６５Ｔ，Ｇ１１６９６Ａ，Ｔ１１７２２Ｃ，Ｔ１１７７０Ｃ，Ｇ１１９６９Ａ，Ａ１２０４０Ｇ，Ｔ１２０９１Ｃ，Ｇ１２１９２Ａ，Ａ１２２３４Ｇ，Ｔ１２３５４Ｃ，Ｔ１２４０８Ｃ，Ｇ１２６２２Ａ，Ｇ１２６３０Ａ，Ａ１２６３４Ｇ，Ｇ１２６５１Ａ，Ｔ１２８０４Ｃ，Ａ１２８３４Ｇ，Ｃ１３０１１Ｔ，Ａ１３０５７Ｇ，Ｔ１３２１５Ｃ，Ａ１３２２１Ｇ，Ｇ１３２２５Ａ，Ｃ１３２５１Ｔ，Ａ１３２６３Ｇ，Ａ１３２６９Ｇ，Ｃ１３３８３Ｔ，Ａ１３４１３Ｇ，Ｔ１３４６１Ｃ，Ａ１３６０６Ｇ，Ａ１３６１４Ｇ，Ｔ１３６１７Ｃ，Ｃ１３６９５Ａ，Ｇ１３８１０Ａ，Ａ１３８８７Ｇ，Ａ１４００１Ｇ，Ａ１４０５３Ｇ，Ｃ１４１４９Ｔ，Ｃ１４１５８Ｔ，Ｃ１４２８１Ｇ，Ｔ１４３１８Ｃ，Ｇ１４５４４Ａ，Ｃ１４８６７Ｔ，Ａ１５２３５Ｇ，Ｇ１５８８４Ａ，１５９４０ｄｅｌ−Ｔ，Ａ１５９７４Ｇ，Ａ１６０３７Ｇ，Ｔ１６０８６Ｃ，Ｃ１６１６９Ｔ，Ｃ１６２０１Ｔ，Ａ１６２１５Ｇ，Ｔ１６２２４Ｃ，Ａ１６２４０Ｇ，Ｃ１６２５７Ｔ，Ｃ１６２６６Ａ，Ａ１６２６９Ｇ，Ｃ１６２７０Ｔ，Ｃ１６２９１Ｇ，Ｃ１６２９２Ｔ，Ｃ１６２９２Ｇ，Ｃ１６２９６Ｔ，Ａ１６３０２Ｇ，Ａ１６３１８Ｔ，Ｃ１６３２０Ｔ，Ｃ１６３２７Ｔ，Ｔ１６３５２Ｃ，Ｃ１６３５５Ｔ，Ｃ１６３６０Ｔ，Ｇ１６４５６Ｃ，Ａ１６５２３Ｇ，Ｃ１６５２７Ｔのうちの少なくとも一つ、または二つ以上の塩基の変異に基づいて、その者が長寿者となるか否かについての判断資料を与えることを特徴とするヒトミトコンドリア遺伝子変異に基づく遺伝子検出法である。これら２０５ヶ所の変異は、百寿者群にのみ見られた変異である。
【００１６】
また、全ての変異のうち、「パーキンソン病患者に認められた多型数／百寿者（岐阜百寿者及び東京百寿者の合計）に認められた多型数」という割合について、適当な範囲（例えば、１．２以上、１．５以上、２．０以上、３．０以上、０．８以下、０．７以下、０．６以下、０．５以下、０．４以下などが例示できる）を選択することにより、ある者がパーキンソン病となる可能性、或いはある者が長寿となる可能性についての判断資料を精度良く与えることもできる。
【００１７】
【発明の実施の形態】
次に、本発明の一実施形態について、図表を参照しつつ詳細に説明するが、本発明の技術的範囲は、下記の実施形態によって限定されるものではなく、その要旨を変更することなく、様々に改変して実施することができる。また、本発明の技術的範囲は、均等の範囲にまで及ぶものである。
【００１８】
＜対象＞
各々９６名のパーキンソン病患者群及び、百寿者群（岐阜地方での１１名と、東京地方での８５名）のミトコンドリアゲノム全塩基配列（１３個のｍＲＮＡ（タンパクコーディング領域）、２２個のｔＲＮＡ、及び２個のｒＲＮＡを含む。図１を参照。）を解析した。なお、全ての被験者は本研究への参加に同意した。また、本研究は名古屋大学総合保健体育科学センターの倫理委員会で承認された。
【００１９】
＜方法＞
各被験者から静脈血２ｍＬを５０ｍＭＥＤＴＡを含有した採血管に集めた。総ＤＮＡは、ＭａｇＥｘｔｒａｃｔｏｒＳｙｓｔｅｍＭＦＸ−２０００（Ｔｏｙｏｂｏ、大阪）を用いて血液から抽出した。ミトコンドリアゲノム全てを既報に示す通り（ＭａｓａｓｈｉＴａｎａｋａ，ＭｉｋａＨａｙａｋａｗａ，ａｎｄＴａｋａｙｕｋｉＯｚａｗａ，ＡｕｔｏｍａｔｅｄＳｅｑｕｅｎｃｉｎｇｏｆＭｉｔｏｃｈｏｎｄｒｉａｌＤＮＡ，ＭｅｔｈｏｄｓｉｎＥｎｚｙｍｏｌｏｇｙ，Ｖｏｌｕｍｅ２６４，４０７−４２１，１９９６：特開平１１−１１３５９７号公報）、１度目のＰＣＲ（ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ，１ｓｔＰＣＲ）で６つの断片を増幅し、その後、２度目のＰＣＲ（２ｎｄＰＣＲ）で互いにオーバーラップする６０の領域を増幅した。
すなわち、ミトコンドリアゲノムは、表１に示したプライマー対（Ｌ１およびＨ１プライマー）を用いたＰＣＲ法により、約３．０ｋｂの領域（フラグメントＡ〜Ｆ）として増幅した。各プライマーの塩基配列は、次の通りである（なお、表１に記載されているプライマーのうち、Ｌ５５４５，ＦＬ８０５３，ＦＬ８６３５，ＦＬ９２１３，ＦＬ１２６００，ＦＬ１６２２１，Ｈ３０８２，Ｈ９２３５，Ｈ３４２を除く各プライマーの塩基配列は、上記既報に開示されているので、重複を避けるため記載を省略する）。Ｌ５５４５は、５’−ＡＣＡＧＣＴＡＡＧＧＡＣＴＧＣＡＡＡＡＣ−３’ （配列番号１）、ＦＬ８０５３は、５’−ＴＧＴＡＡＡＡＣＧＡＣＧＧＣＣＡＧＴＡＣＡＡＧＡＣＧＴＣＴＴＧＣＡＣＴＣＡＴ−３’（配列番号２）、ＦＬ８６３５は、５’−ＴＧＴＡＡＡＡＣＧＡＣＧＧＣＣＡＧＴＣＴＣＡＴＣＡＡＣＡＡＣＣＧＡＣＴＡＡＴ−３’（配列番号３）、ＦＬ９２１３は、５’−ＴＧＴＡＡＡＡＣＧＡＣＧＧＣＣＡＧＴＣＡＣＣＡＡＴＣＡＣＡＴＧＣＣＴＡＴＣＡ−３’（配列番号４）、ＦＬ１２６００は、５’−ＴＧＴＡＡＡＡＣＧＡＣＧＧＣＣＡＧＴＡＴＴＣＡＴＣＣＣＴＧＴＡＧＣＡＴＴＧＴ−３’（配列番号５）、ＦＬ１６２２１は、５’−ＴＧＴＡＡＡＡＣＧＡＣＧＧＣＣＡＧＴＣＣＣＴＣＡＡＣＴＡＴＣＡＣＡＣＡＴＣＡ−３’（配列番号６）、Ｈ３０８２は、５’−ＴＡＧＡＡＡＣＣＧＡＣＣＴＧＧＡＴＴＡＣ−３’（配列番号７）、Ｈ９２３５は、５’−ＴＣＡＴＧＧＧＣＴＧＧＧＴＴＴＴＡＣＴＡ−３’（配列番号８）、Ｈ３４２は、５’−ＴＴＴＴＴＧＧＧＧＴＴＴＧＧＣＡＧＡＧＡ−３’（配列番号９）である。
【００２０】
【表１】

【００２１】
ＰＣＲ法の条件は、９４℃で５分間の熱変性から開始し、９４℃で１５秒の熱変性、６０℃で１５秒のアニーリング、および７２℃で３分の伸長反応を４０サイクル行い、最後に７２℃で１０分の伸長反応を行った。１ｓｔＰＣＲ増幅産物は、１％アガロースゲルで電気泳動した後、エチジウムブロマイドで視覚化することにより確認した。
その後、フラグメントＡ〜Ｆを表１に示したプライマー対（ＦＬ２およびＨ２プライマー）を用いたＰＣＲ法により、約６００〜１０００ｂｐの６０の小領域に分けて増幅した（２ｎｄＰＣＲ）。２ｎｄＰＣＲのフォーワード（Ｆｏｒｗｏｒｄ）プライマーは、３８塩基のオリゴヌクレオチドであり、２０塩基のＬ鎖特異的な配列の５’末端側に、ユニバーサルシークエンスプライマー（−２１Ｍ１３，５’−ＴＧＴＡＡＡＡＣＧＡＣＧＧＣＣＡＧＴ−３’：配列番号１０）の配列１８塩基を結合したものである。ＰＣＲ法の条件は、９４℃で１５秒の熱変性、６０℃で１５秒のアニーリング、および７２℃で３分の伸長反応を４０サイクル行い、その後７２℃で１０分の伸長反応を行った。これらの２ｎｄＰＣＲＤＮＡは、ＭｕｌｔｉＳｃｒｅｅｎーＰＣＲプレート（Ｍｉｌｌｉｐｏｒｅ，Ｂｅｄｆｏｒｄ，ＭＡ）を用いて精製した。精製後のＤＮＡの質は、Ｒｅａｄｙ−Ｔｏ−ＲｕｎＳｅｐａｒａｔｉｏｎＵｎｉｔ（ＡｍｅｒｓｈａｍＰｈａｒｍａｃｉａＢｉｏｔｅｃｈＡＢ，ＳａｎＦｒａｎｃｉｓｃｏ，ＣＡ）を用いたエチジウムブロマイドを含む１．５％アガロースゲル電気泳動で確認した。
【００２２】
シークエンス反応は、２ｎｄＰＣＲＤＮＡ、−２１Ｍ１３ユニバーサルプライマー、およびＢｉｇＤｙｅＴｅｒｍｉｎａｔｏｒＣｙｃｌｅＳｅｑｕｅｎｃｅＲｅａｄｙＲｅａｃｔｉｏｎＫｉｔ１．０または３．０（ＡｐｐｌｉｅｄＢｉｏｓｙｓｔｅｍｓ，ＦｏｓｔｅｒＣｉｔｙ，ＣＡ）を用いて行った。ＰＣＲ条件は、まず９６℃で５分間の熱変性をし、次に９６℃で１０秒の熱変性、５０℃で５秒のアニーリング、および６２℃で３分の伸長反応を２５サイクル行い、最後に６２℃で３分の伸長反応を行った。シークエンス反応の後、過剰なＤｙｅＴｅｒｍｉｎａｔｏｒをＭｕｌｔｉＳｃｒｅｅｎ−ＰＣＲＨＶプレート（Ｍｉｌｌｉｐｏｒｅ）を用いたゲルろ過によって除去した。精製されたＤＮＡサンプルは、乾燥させた後にｔｅｍｐｌａｔｅｓｕｐｐｒｅｓｓｉｏｎｒｅａｇｅｎｔ（ＴＳＲ，ＡｐｐｌｉｅｄＢｉｏｓｙｓｔｅｍｓ）、またはホルムアミド（ＡｐｐｌｉｅｄＢｉｏｓｙｓｔｅｍｓ）に溶解させた。溶解させたＤＮＡサンプルは、９５℃で２分間熱変性させ、直ちに氷上に移した。ＤＮＡシークエンスは、自動ＤＮＡシークエンサー３１０または３７７（ＡｐｐｌｉｅｄＢｉｏｓｙｓｔｅｍｓ）を用いて分析した。
シークエンス解析は、ＳｅｑｕｅｎｃｉｎｇＡｎａｌｙｓｉｓＰｒｏｇｒａｍｖｅｒｓｉｏｎ４．１（ＡｐｐｌｉｅｄＢｉｏｓｙｓｔｅｍｓ）を用いて行った。シークエンス断片は、シークエンス解析ソフトウェアＳｅｑｕｅｎｃｈｅｒ３．１．１（ＧｅｎｅＣｏｄｅｓ，ＡｎｎＡｒｂｏｒ，ＭＩ）を用いて整列させ、一塩基変異多型（以下、「ＳＮＰ」（ｓｉｎｇｌｅｎｕｃｌｅｏｔｉｄｅｐｏｌｙｍｏｒｐｈｉｓｍｓ）という）の場所の同定に用いた。各々のＳＮＰは目で再確認した。なお、ＤＮＡの増幅は、互いにオーバーラップさせたので、少なくても２つの領域で各々のＳＮＰを確認した。
【００２３】
各々のｍｔＤＮＡ配列は、オリジナルケンブリッジリファレンスシークエンス（ｏＣＲＳ）及び改訂版ケンブリッジリファレンスシークエンス（ｒＣＲＳ）（ＡｎｄｒｅｗｓＲ．Ｍ．，ＫｕｂａｃｋａＩ．，ＣｈｉｎｎｅｒｙＰ．Ｆ．，ＬｉｇｈｔｏｗｌｅｒｓＲ．Ｎ．，ＴｕｒｎｂｕｌｌＤ．Ｍ．，ＨｏｗｅｌｌＮ．ＲｅａｎａｌｙｓｉｓａｎｄｒｅｖｉｓｉｏｎｏｆｔｈｅＣａｍｂｒｉｄｇｅｒｅｆｅｒｅｎｃｅｓｅｑｕｅｎｃｅｆｏｒｈｕｍａｎｍｉｔｏｃｈｏｎｄｒｉａｌＤＮＡ．ＮａｔＧｅｎｅｔ１９９９；２３：１４７．）と比較した。
【００２４】
＜結果＞
１．日本人におけるコンセンサスシークエンス（Ｊａｐａｎｅｓｅｃｏｎｓｅｎｓｕｓｓｅｑｕｅｎｃｅ（ＪＣＳ））
本研究において、ＳＮＰはｒＣＲＳとの比較により解析したが、その頻度が１００％、若しくはそれに近い場合には、その塩基配列を日本人におけるコンセンサスシークエンス（ＪＣＳ）とし、標準塩基配列として用いた（表２）。
【００２５】
【表２】

【００２６】
２．塩基置換、挿入、および欠失数について
９６名のパーキンソン病患者において、ミトコンドリアゲノム全体で５５７個の多型が見つかり、蛋白質コーディング領域では３４８カ所に多型があった。その内、２４４カ所（７０．１％）は同義置換（ｓｙｎｏｎｙｍｏｕｓｓｕｂｓｔｉｔｕｔｉｏｎ；塩基置換がアミノ酸の置換を伴わないもの）であり、１０４カ所（２９．９％）は非同義置換（ｎｏｎｓｙｎｏｎｙｍｏｕｓｓｕｂｓｔｉｔｕｔｉｏｎ；塩基配列がアミノ酸の置換を伴うもの）であった。また、２個のｒＲＮＡ及び２２個のｔＲＮＡの塩基置換（置換、挿入、および欠失）は、７３ヶ所で認められた。さらに、非コーディング領域においては、１３６カ所に多型が見つかった。
９６名の百寿者において、ミトコンドリアゲノム全体で５１９個の多型が見つかり、蛋白質コーディング領域では３２７カ所に多型があった。その内、２３１カ所（７０．６％）が同義置換であり、９６カ所（２９．４％）が非同義置換であった。また、２個のｒＲＮＡ及び２２個のｔＲＮＡの塩基変異（置換、挿入、および欠失）は、５６ヶ所で認められた。さらに、非コーディング領域においては、１３５カ所に多型が見つかり、Ｌ鎖複製開始領域で、１カ所の多型があった。
【００２７】
表３〜表２２には、コーディング領域、ＲＮＡ遺伝子領域、及び非コーディング領域において、パーキンソン病患者及び百寿者に確認された変異（置換、挿入、及び欠失）の全てを示した。
（１）タンパク質コーディング領域において、パーキンソン病患者群および百寿者群の間に生じた同義置換の頻度比較について、表３〜表１０に示した。
【００２８】
【表３】

【００２９】
【表４】

【００３０】
【表５】

【００３１】
【表６】

【００３２】
【表７】

【００３３】
【表８】

【００３４】
【表９】

【００３５】
【表１０】

【００３６】
（２）タンパク質コーディング領域における非同義置換の頻度について、表１１〜表１４に示した。
【表１１】

【００３７】
【表１２】

【００３８】
【表１３】

【００３９】
【表１４】

【００４０】
（３）また、パーキンソン病患者群および百寿者群の両群から検出された２個のｒＲＮＡ、及び２２個のｔＲＮＡにおける塩基置換について、表１５〜表１７に示した。
【表１５】

【００４１】
【表１６】

【００４２】
【表１７】

【００４３】
（４）パーキンソン病患者群及び百寿者群の両群から検出されたメジャー非コード領域（Ｍａｊｏｒｎｏｎ−ｃｏｄｉｎｇｒｅｇｉｏｎ）、Ｌ鎖複製領域（ｏｒｉｇｉｎｏｆＬ−ｓｔｒａｎｄｒｅｐｌｉｃａｔｉｏｎ）、及びマイナー非コード領域（Ｍｉｎｏｒｎｏｎ−ｃｏｄｉｎｇｒｅｇｉｏｎ）における塩基置換を表１８〜表２２に示した。
【表１８】

【００４４】
【表１９】

【００４５】
【表２０】

【００４６】
【表２１】

【００４７】
【表２２】

【００４８】
３．Ｌ鎖複製開始点の塩基置換
１名の百寿者でＬ鎖複製開始点の近傍にＧ５７４４Ａが認められた（表１９）。
なお、必要であれば、これらの表から、パーキンソン病者群でのみ認められる変異、百寿者群よりもパーキンソン病者群において高い頻度で認められる変異、百寿者群でのみ認められる変異、及びパーキンソン病者群よりも百寿者群において高い頻度で認められる変異（更には、それらの変異のうち、同義置換または非同義置換）を容易に抽出することができる。
このように本実施形態によれば、（１）ある者がパーキンソン病となる可能性があるか否か、或いは、（２）ある者が健康長寿となる可能性があるか否かに関して、有用な情報を与える遺伝子検出法を提供することができる。また、本実施形態によれば、適当な分野において、個人識別を行える方法を提供できる。
【００４９】
【配列表】

【図面の簡単な説明】
【図１】ヒトミトコンドリアＤＮＡの遺伝子の配置を示す図である。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a human mitochondrial DNA (mtDNA) polymorphism, a detection method that uses the mtDNA polymorphism to provide useful information as to whether or not a person can have Parkinson's disease, The present invention can be applied to a detection method that gives useful information as to whether or not longevity can be obtained, or an individual identification method (for example, forensic medicine, paternity testing, epidemiological investigation, archeological investigation, and the like).
[0002]
[Prior art]
Parkinson's disease is considered to be a multifactorial disease involving a genetic predisposition. Research on genetics and analysis of candidate genes for Parkinson's disease has shown dramatic progress along with the progress of human gene analysis programs.
On the other hand, there are many people who are healthy and enjoy longevity, such as centenarians who are over 100 years old at full age. These centenarians may have specific genetic polymorphisms.
[0003]
It is known that a human mitochondrial gene (hereinafter referred to as mtDNA) is present in mitochondria and carries out maternal inheritance. In mitochondria, since reactions related to energy metabolism are mainly performed, it is considered that they are related to healthy and long-lived persons and some Parkinson's disease.
The present inventors have been continuously conducting studies on mtDNA polymorphisms (for example, Japanese Patent Application Laid-Open No. 11-113597), and have determined a detailed relationship between mtDNA polymorphisms, healthy long-lived people, and Parkinson's disease. The analyzed prior art is not confirmed.
[Patent Document 1] JP-A-11-113597
[0004]
[Problems to be solved by the invention]
Since genomic polymorphisms vary depending on race and ethnicity, it is important to construct a database of mitochondrial genomic polymorphisms related to Parkinson's disease in each ethnicity and ethnic group, and a mitochondrial genomic polymorphism database related to healthy life expectancy. .
The present invention has been made in view of the above circumstances, and aims to contribute to prevention and diagnosis of Parkinson's disease by searching for mitochondrial genomic polymorphisms between Parkinson's disease patients and long-lived people, and Another object is to find polymorphisms associated with longevity, and to provide a method for identifying individuals based on mitochondrial genomic polymorphisms.
[0005]
Means for Solving the Problems, Effects of the Invention, and Effects of the Invention
The present inventors deciphered the entire nucleotide sequence (16569 base pairs) of human mitochondrial DNA of 96 Parkinson's disease patients and 100 life persons (who had a life expectancy of 99.1 years or more at full age). By analyzing mutations (substitutions, deletions, additions), the present invention was basically completed.
By comparing the mutations in human mitochondrial DNA in both groups, it is possible to provide data for determining (1) those who are at high risk of developing Parkinson's disease, (2) those who are highly likely to have longevity, etc. it can. Individual identification can also be performed based on the mutations detected in both groups.
[0006]
That is, in order to solve the above-mentioned problems, the first invention is directed to a human mitochondrial DNA in which 42ins-C, T63C, C64T, 66del-G, G68A, A73G, A93G, G94A, G103A, T131C, T146C, C150C, C150C, T150C, C150C, and C150C , T152C, A153G, A183G, G185A, A189G, 190ins-A, A191G, A193G, C194T, T195C, T196C, C198T, T199C, A200G, A202G, G203A, T204C, G207A, A210G, A211G, A214G, G228A, A235G, 248del -A, T252C, A257G, G260A, A263G, T279C, C280T, 281G, A284G, 286del-A, 287del-A, C298T, 310ins-C, C325T, C348G, C348T, A351C, A368G, G380C, C382T, A385T, A385T, A385T, A385T, A385T, A385T, A385T, A385T T489C, G499A, T504C, C506T, G513A, C530T, A533G, 540ins-C, A546G, C552T, A663G, T681C, G709A, C752T, A827G, A856G, T961C, C983T, C984T, A998G, A1041G, C1048T, T1107C, A1118G, T1119C, A1148G, G1211A, C1310T, A1382C, T1420C, A1438G, G1442A, G1598A, G1664A, G1709A, G1719A, C1734T, A1736G, T1819C, T1822C, G1888A, T1977C, 2150ins-A, A2178G, A2220G, A2246G, C2263A, T2330C, T2416C, T2626C, A2706G, C2766T, C2772T, G2831A, C2835T, T2863C, T2887C, G3010A, 3106del-C, 3107del-C, A3145G, C3204T, C3206T, A3221G, A3221G 338C, G3391A, T3394C, A3397G, T3423C, C3442T, T3456C, G3496T, C3497T, A3520G, A3537G, T3552C, T3552A, G3591A, T3644C, C3696T, A3720G, A3759G, A3768G, T3826C, A3873G, G3882A, C3960T, C3963A, C3970T, T4047C, G4048A, T4062C, C4071T, C4086T, G4092A, G4113A, T4117C, A4131G, A4164G, A4203G, T4209C, T4232C, T4248C, C4251T, A4310G, A4343G, T4386C, C4394 , G4491A, C4505T, G4541T, T4612C, G4655A, G4659A, C4670T, T4688C, T4705C, A4715G, A4732G, T4736C, T4742C, A4769G, A4793G, G4820A, A4824G, A4833G, C4850T, T4859C, C4883T, A4895G, G4924A, C4926T, A4958G , T5048C, C5049T, G5054A, T5108C, A5127G, A5128G, G5147A, A5153G, C5178A, T5201C, G5231A, G5237A, A5240G, C5321A, A5240G, C5261A 379T, G5417A, A5441G, T5442C, G5460A, T5465C, G5471A, T5492C, A5539G, C5601T, T5628C, T5655C, G5744A, G5773A, T5788C, G5821A, T5826C, T5826C, A5894G, A5900C, A5951G, T5964C, G5979A, G6018A, G6023A, G6026A, A6039G, C6053T, A6146G, G6179A, T6185C, T6221C, C6242T, T6253C, G6261A, T6278C, A6299G, G630T, A6332G, A6332G, A6332G, A6332G, A6332G, A6332. , C6452T, C6455T, C6483T, T6512C, T6524C, A6533G, C6542T, C6569A, A6575G, T6614C, T6620C, T6641C, C6644T, T6671C, T6680C, C6689T, A6698G, T6719C, A6737G, A6752G, C6761T, G6899A, G6962A, C6983T, C7028T , T7058C, T7142C, A7146G, T7191C, C7196A, C7214T, T7220C, C7322T, C7235T, C7244T, C7256T, T7258C, T7270C, C735T, C7389, A7352T, T7320C, A7352T, T7320C , G7521A, G7598A, G7600A, A7673G, T7684C, T7738C, A7755G, C7774T, C7810T, A7822G, G7853A, T7861C, C7867T, C7868T, C7891T, C7909T, G7912A, C7927T, T7961C, G8020A, A8021G, T8063C, A8071G, A8074G, C8140T , A8149G, T8167A, T8167C, A8188G, T8200C, C8203T, G8206A, A8225G, T8227C, G8251A, T8265C, C8270T, G8283A, C8291G, A82931G, A82931G, A82913G 413G, C8414T, T8419C, C8429A, T8450C, C8455T, C8461T, A8470G, T8473C, A8489G, A8537G, A8537G, G8557A, G8557A, A8563G, A8563G, G8572A, G8584A, C8595T, T8610C, T8654C, A8664G, C8684T, A8701G, T8762C, A8784G, C8788T, C8794T, A8812G, C8829T, C8844T, G8854A, A8860G, A8894T, C8905A, A8929G, C8964T, G8994A, T9017G, 9090G, 9090G, 9090G , C9099A, A9115G, G9123A, T9128C, C9129T, T9165C, T9174C, A9180G, A9242G, A9288G, C9293T, C9296T, A9299G, G9305A, A9341T, A9377G, T9386C, C9431T, G9477A, T9479C, A9494G, C9536T, T9540C, A9545G, G9548A , G9575A, G9612A, A9667G, T9750C, G9755A, G9804A, C9812T, T9824C, T9824A, T9833C, T9836G, A9843G, G99T9C, G9921C, G9932A, G9932A 977C, T10084C, C10104T, G10172A, C10181T, T10238C, T10274C, G10310A, T10345C, G10373A, A10397G, A10398G, C10400T, T10410C, A10411G, T10609C, C10637T, G10646A, A10750G, T10790C, G10801A, T10873C, A10876G, T10915C, C10954T, A10972G, C10976T, G11016A, T11017C, A11020G, C11059T, A11084G, T11087C, T11113C, C11146T, G11149A, C11151T, A11167G, C11215 , T11437C, A11530G, C11536T, C11647T, C11665T, G11696A, T11701C, G11719A, T11722C, T11770C, T11854C, G11914A, T11944C, A11959G, G11969A, G12007A, A12026G, A12030G, A12040G, C12084T, C12088T, T12091C, C12092A, G12192A, A12210G , A12234G, T12311C, T12354C, A12358G, A12361G, G12372A, T12396C, A12397G, C12405T, G12406A, T12408C, T12468C, G12622A, G1622A. 2630A, C12633T, A12634G, G12651C, G12651A, C12705T, G12771A, T12804C, T12811C, C12816T, A12834G, T12880C, C12882T, C13011T, A13050G, C13053G, A13057G, A13104G, A13105G, C13110T, G13135A, T13143C, T13215C, A13221G, T13224C, G13225A, C13251T, A13263G, A13269G, A13278G, T13281C, C13338T, G13359A, C13383T, A13395G, A13413G, A13434G, T13461C, T1500. C, A13563G, G13590A, A13606G, A13614G, T13617C, A13629G, A13651G, C13695A, G13708A, G13759A, T13768C, G13810A, A13827G, T13879C, A13887G, G13928A, G13928C, A14001G, A14002G, G14016A, A14053G, C14082T, A14091G, A14133G, C14149T, C14158T, A14161G, G14162A, T14180C, A14185T, G14198A, T14200C, G14226A, C14281T, C14281G, T14287C, T14308C, T14318C. 4325C, G14364A, C14365G, T14371C, T14386C, C14389T, A14417G, T14470C, G14476A, G14544A, A14548G, C14562G, G14569A, A14582G, A14605G, C14668T, A14693G, A14696G, A14750G, C14766T, T14783C, C14867T, C14944T, T14979C, G15043A, T15067C, G15148A, A15218G, C15223T, A15235G, A15236G, G15301A, G15314A, G15323A, A15326G, C15331A, G15346A, G1555A C, T15479C, A15487T, G15497A, C15508T, C15518T, A15524G, C15535T, A15662G, T15670C, A15724G, A15758G, T15784C, T15850C, A15851G, A15860G, A15874G, G15884A, A15924G, G15927A, T15940-, T15941C, A15951G, A15954G, A15974G , G16000A, A16037G, A16051G, T16075C, T16086C, T16092C, T16093C, T16094C, C16111T, T16126C, G16129A, T16136C, T16140C, G16140C 16154C, A16162G, A16164G, C16168T, C16169T, T16172C, C16173T, C16174T, C16176T, A16183C, T16189C, C16201T, T16209C, C16214G, A16215G, A16216G, T16217C, C16223T, T16224C, A16227G, C16232A, C16234T, A16235G, A16240G, T16243C, G16244A, C16245T, T16249C, A16252C, A16254G, C16256T, C16257A, C16257T, A16258T, 16258ins-C, C16260T, C16261T, T16263C 6265G, C16266T, C16266A, C16268T, A16269G, C16270T, G16274A, C16278T, A16284G, C16287T, T16288C, C16290T, C16291T, C16291G, C16292T, C16292G, C16294T, C16295T, C16296T, T16297C, 16298ins-A, T16298C, A16299G, A16300G, A16302G, T16304C, A16309G, T16311C, A16316G, A16317G, A16318T, G16319A, C16320T, T16324C, T16325C, C16327T, T16342C. 352C, C16355T, T16356C, T16357C, C16360T, T16362C, A16367C, T16368C, G16373A, T16381C, G16390A, A16399G, C16400T, G16456C, A16463G, A16497G, T16519C, A16523G, at least one of C16527T or two or more bases, This is an individual identification method based on human mitochondrial gene mutation, characterized in that individual identification is performed based on the mutation of the above.
[0007]
557 mutations were confirmed in the Parkinson's disease patient group, and 519 mutations were confirmed in the centenarian group. The 762 mutations described above are all except for those duplicated positions.
In the present invention, the term “mutation” refers to a so-called “revised Cambridge standard sequence” or a mutation in a specific base compared to the consensus sequence in Japanese (JCS: see Table 2) found by the present inventors. Means that. In this specification, “mutation” includes substitution, insertion, or deletion of a base.
Further, in this specification, regarding the base substitution, (1) a state in which two alphabetic characters sandwich an arrow (→) after a number, or (2) a state in which two types of alphabetic characters sandwich a number Indicated by. In the case of the above (1), the numeral indicates the position where the base substitution has been performed, and the first English letter indicates the base before the substitution and the subsequent English letter indicates the base after the substitution. For example, “10235T → C” indicates that thymine at position 10235 has been mutated to cytosine. In the case of the above (2), the numeral indicates the position where the base substitution was performed, the first alphabetic character indicates the base before substitution and the subsequent English character indicates the base after substitution. For example, “T3336C” indicates that thymine at position 3336 has been mutated to cytosine.
[0008]
For the base insertion, for example, "ins" indicating the meaning of the insertion is indicated by a numeral indicating the position where the insertion was made, such as "7465ins-C" or "7465C-ins". And the bases described. Regarding the base deletion, for example, "248 del-A" or "248 A del" indicates the position where the deletion was made by a numeral, followed by "del" indicating the meaning of the deletion, and "deletion" And the bases described.
In addition, amino acid substitutions are indicated by the type of protein and two types of English characters (three-letter amino acid notation) with symbols interposed between numbers. In this case, the meaning of the letters and numbers is such that the first letter indicates the amino acid before substitution, and the last letter indicates the amino acid after substitution. The numbers indicate the positions where amino acid substitutions are made in the target protein. For example, "Cytb, Leu237Phe" means that in Cytb, the 237th leucine is substituted with phenylalanine.
[0009]
“Hvr” means a hypervariable region, and there are two places, hvr1 (303-317) and hvr2 (16180-16195). Further, “W” means a wild-type nucleotide sequence (Wild-type sequence), which is a standard revised Cambridge Reference Sequence (rCRS, revised Cambridge reference sequence; Andrews R.M., Kubancha. PF, Lighttowers RN, Turnbull DM, Howell N. Realization and review of the Cambridge reference sequence, the same sequence as in the case of the same sequence as in the case of the same sequence as in the case of the above-mentioned sequences. . As positions marked with “W”, the high frequency mutation site 1 (hvr1-303-317) is “W303-317hvr1”, the CA repeat (CA-514-523) is “W514insCA2” or “W514delCA2”, and the C stretch 1 ( C1-568-573) is “W568Cn-ins”, 12S rRNA (956-965) is “W956Cn-ins”, C stretch 2 (C2-5895-5899) is “W5895Cn-ins”, 9 bp deletion / insertion ( 9-bp del / ins-8272-8289) may be referred to as “W8272-del”, and the hypermutation site 2 (hvr2-16180-16195) may be referred to as “W16180-95-hvr2”. These sites are highly mutated between rCRS and each individual (or even between individuals).
[0010]
Methods for detecting gene mutation include methods known to those skilled in the art, for example, DNA sequencing, multiplex APLP, hybridization using DNA microarray, Invader method, Taqman probe method, Masscode tag method, allele-specific PCR. Methods, RFLP method, various solid-phase fluorescence mini-sequencing methods, immunization sequence-specific oligonucleotide probe assays, and the like, but are not limited to these methods, and may be various types to be developed in the future. DNA analysis can be used.
According to the first aspect, personal identification can be performed based on a mutation in human mitochondrial DNA.
[0011]
The second invention is the human mitochondrial DNA, 42ins-C, C64T, G68A, A73G, T131C, T146C, C150T, T152C, A153G, A183G, G185A, A189G, 190ins-A, A193G, C194T, T195C, T196C, C198T , T199C, A200G, A202G, G203A, T204C, G207A, A211G, A214G, G228A, A235G, 248del-A, T252C, G260A, A263G, T279C, A284G, C298T, C325T, C348G, T408G, T408A, C431T, C441T, 451ins -T, C456T, T489C, G499A, T 04C, G513A, C530T, 540ins-C, C552T, A663G, T681C, G709A, C752T, A827G, T961C, C984T, A1041G, C1048T, T1107C, A1118G, T1119C, A1148G, G1211A, C1310T, A1382C, A1438G, G1442A, G1598A, G1664A, G1709A, G1719A, A1736G, T1819C, T1822C, G1888A, T1977C, 2150ins-A, A2178G, A2220G, A2246G, A2246C, T2326C, T2330C, T2330C 5T, T2863C, G3010A, 3106del-C, 3107del-C, A3145G, C3204T, C3206T, A3221G, T3278C, G3316A, A3327G, T3336C, G3391A, T3394C, A3397G, T3423C, C3442T, G3496T, C3497T, A3537G, T3552C, T3644C, A3720G, A3759G, A3873G, C3960T, C3970T, T4047C, G4048A, C4071T, C4086T, G4092A, G4113A, T4117C, A4131G, C4, T4, C4, T4, A4164G, A4164G, A4164G, A4164G, A4164G, A4164G, A4164G, A4164G 4386C, C4394T, G4491A, C4505T, G4541T, G4655A, C4670T, A4715G, A4732G, T4736C, T4742C, A4769G, A4793G, G4820A, A4824G, A4833G, T4859C, C4883T, A4895G, G4924A, C4926T, A4958G, T5048C, C5049T, G5054A, T5108C, A5128G, G5147A, A5153G, C5178A, T5201C, G5231A, G5237A, A5240G, G5261A, C5263T, A5301G, A5351G, A5351A, G535A, G535A, G535A, G535A, G535A A, C5601T, T5655C, G5773A, G5821A, T5826C, T5826C, A5894G, A5900C, A5951G, G6018A, G6023A, G6026A, A6039G, G6179A, T6185C, T6221C, T6253C, T6278C, G6305A, T6392C, C6410T, T6413C, C6455T, A6533G, A6575G, T6614C, T6620C, C6644T, T6671C, T6680C, C6689T, T6719C, A6737G, A6752G, C6761T, G6899A, G6962A, C6983T, C7028T, T7058C, T7142C, C7196A, C7214T, 7220C, C7232T, C7235T, C7256T, T7258C, A7403G, 7502del-C, G7521A, G7600A, A7673G, T7684C, C7774T, A7822G, G7853A, T7861C, C7867T, C7909T, G7912A, C7927T, G8020A, T8063C, A8071G, A8149G, T8167A, A8188G, T8200C, G8206A, A8225G, T8227C, G8251A, C8297G, A8308G, T8383C, C8414T, T8419C, C8429A, T8450C, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G, A8470G 572A, G8584A, C8595T, T8610C, A8664G, C8684T, A8701G, T8762C, C8794T, C8829T, G8854A, A8860G, A8894T, C8905A, A8929G, C8964T, G8994A, A9041G, G9053A, T9090C, A9115G, G9123A, T9128C, T9165C, T9174C, A9180G, A9242G, A9288G, C9296T, G9305A, A9377G, T9386C, C9431T, G9777A, A9494G, T9540C, G9548A, G9575A, G9612A, G9612A, G9612A, G9612A, G9612A, G9612A, G9612A, G9612A, G9612A, G9612A C, T9836G, G9921A, G9932A, T9938C, T9950C, T9959C, T9977C, T10084C, C10104T, C10181T, T10238C, G10310A, T10345C, G10373A, A10397G, A10398G, C10400T, T10410C, A10411G, T10609C, C10637T, G10646A, A10750G, T10790C, G10801A, T10873C, T10915C, C10954T, C10976T, G11016A, T11017C, A11020G, A11084G, T11087C, A11167G, C11215T, A11530G, C11536T, C11647T. T11701C, G11719A, T11854C, G11914A, T11944C, A11959G, G12007A, A12026G, A12030G, C12084T, C12088T, C12092A, A12210G, T12311C, A12358G, A12361G, G12372A, T12396C, A12397G, C12405T, G12406A, T12468C, C12633T, G12651C, C12705T, G12771A, T12811C, C12816T, T12880C, C12882T, A13050G, C13053G, A13104G, A13105G, C13110T, G13135A, T13143C, T13224C, A13 78G, T13281C, C13338T, G13359A, A13395G, A13434G, T13500C, A13563G, G13590A, A13629G, A13651G, G13708A, G13759A, T13768C, A13827G, T13879C, G13928C, G13928A, A14002G, G14016A, C14082T, A14091G, A14133G, A14161G, G14162A, T14180C, A14185T, G14198A, T14200C, G14226A, C14281T, T14287C, T14308C, T14325C, G14364A, C14365G, T14371C, T14386C. A14417G, T14470C, G14476A, A14548G, C14562G, G14569A, A14582G, A14605G, C14668T, A14693G, A14696G, A14750G, C14766T, T14783C, C14944T, T14979C, G15043A, T15067C, G15148A, A15218G, C15223T, A15236G, G15301A, G15314A, G15323A, A15326G, C15331A, G15346A, G15355A, T15440C, T15479C, A15487T, G15497A, C15508T, C15518T, A15524G, C15535T, A1562G 670C, A15724G, A15758G, T15784C, T15850C, A15851G, A15860G, A15874G, A15924G, G15927A, T15941C, A15951G, A15954G, G16000A, A16051G, T16075C, T16092C, T16093C, T16094C, C16111T, T16126C, G16129A, T16136C, T16140C, G16145A, T16154C, A16162G, A16164G, C16168T, T16172C, C16173T, C16174T, C16176T, A16183C, T16189C, T16209C, C16214G, A16216G , C16223T, A16227G, C16232A, C16234T, A16235G, T16243C, G16244A, C16245T, T16249C, A16252C, A16254G, C16256T, C16257A, A16258T, 16258ins-C, C16260T, C16261T, T16263C, A16265G, C16266T, C16268T, G16274A, C16278T, A16284G , C16287T, T16288C, C16290T, C16291T, C16294T, C16295T, T16297C, T16298C, 16298ins-A, A16299G, A16300G, T16304G, A1630C 1C, A16316G, A16317G, G16319A, T16324C, T16325C, T16342C, C16344T, T16356C, T16357C, T16362C, A16367C, T16368C, G16373A, T16381C, G16390A, A16399G, C16400T, A16463G, A16497G, at least one of T16519C or two, A gene detection method based on a mutation in a human mitochondrial gene, which is characterized by giving judgment data on whether or not a person has Parkinson's disease based on mutation of one or more bases.
[0012]
In the Parkinson's disease patient group, 557 mutations were confirmed. In the second invention, by detecting any one (one or two or more) of these 557 mutations, data for judging whether or not the person has Parkinson's disease can be given. .
Note that in the second invention, preferably, T131C, T146C, C150T, A153G, A189G, T195C, G207A, A214G, C298T, C431T, G709A, A827G, A17G, A17G, A17G, A1727, A127C, A127C , T4386C, A4715G, A4732G, A4793G, A4833G, T4859C, A4895G, A4958G, C5049T, T5108C, G5147A, G5231A, G5417A, T5465C, G5773A, T6185C, T6253C, C6410T, C6689T, A6752G, C7028T, C7196A, C786 T, T8200C, A8701G, T9090C, G9123A, T9540C, C10181T, G10373A, C10400T, T10873C, C10976T, T11017C, A11084G, C11215T, G11719A, G11914A, A12358G, G12372A, C12705T, G12771A, T12880C, A13104G, G14364A, T14371C, G14476A, G14569A, T14783C, G15043A, T15067C, G15301A, G15323A, T15440C, A15487T, G15497A, C15535T, T15784C, T15850G, A15860G, A15860G. C, A15951G, A15954G, T16092C, C16111T, T16126C, T16209C, T16217C, C16223T, C16232A, C16234T, G16244A, C16257A, C16260T, C16261T, G16274A, C16287T, C16291T, T16298C, T16324C, T16325C, A16463G, at least one of A16497G It can be based on one or more base mutations.
According to the analysis of the present inventors, 104 mutations were found more frequently in Parkinson's disease patients than in those with 100% life expectancy (mutations were observed in both the 100 years old and Parkinson's disease patients, and By confirming the presence or absence of a large number of mutations), it is possible to provide judgment data on whether or not the person is highly likely to be a Parkinson's disease patient.
[0013]
Further, in the second invention, preferably, 42ins-C, A183G, G185A, A193G, T196C, C198T, G203A, A211G, G228A, T252C, T279C, T284G, C348G, C348G, C348G, C348T , G513A, C530T, 540ins-C, C552T, T961C, C984T, A1041G, A1118G, G1211A, G1664A, G1709A, T1819C, T1822C, A2178G, A2220G, C2263A, T2330C, T2416C, C2835T, T2863C, 3107del-C, A3145G, C3204T , A3221G, A3327 G, T3336C, A3397G, T3423C, C3442T, T3552C, T3644C, A3720G, A3873G, C3960T, T4047C, G4092A, G4113A, A4131G, A4203G, T4232C, C4251T, G4491A, G4541T, C4670T, T4736C, T4742C, G4924A, C4926T, T5048C, G5054A, A5128G, T5201C, G5237A, A5240G, G5261A, C5263T, A5351C, A5441G, G5471A, T5655C, G5821A, T5826C, T5826C, T5826C60, T5826C, T5826C60 6278C, G6305A, A6533G, A6575G, T6614C, C6644T, T6671C, T6719C, C6761T, G6899A, C6983T, T7058C, T7142C, C7214T, T7220C, C7235T, T7258C, 7502del-C, A7673G, C7774T, T7861C, C7909T, C7927T, T8063C, A8149G, T8167A, A8188G, A8225G, T8227C, C8297G, A8308G, T8383C, T8419C, C8429A, A8470G, A8537G, A8537G, A8537G, A8537G, A8537G, A8537G, A8537C, G8572A, C8572A 894T, C8905A, A8929G, A9041G, A9115G, T9174C, A9242G, A9288G, G9305A, T9386C, C9431T, G9477A, G9612A, T9833C, T9836G, G9921A, G9932A, T9938C, T9959C, T9977C, T10084C, T10238C, A10411G, C10637T, G10646A, A10750G, T10790C, T10915C, C10954T, G11016A, A11020G, T11087C, A11167G, A11530G, T11701C, T11854C, A11959G, A12030G, C12092T, C12092T, C12092T T12396C, A12397G, T12468C, C12633T, C12816T, A13050G, C13053G, T13143C, T13224C, T13281C, C13338T, G13359A, A13395G, A13434G, T13500C, A13629G, T13879C, G14016A, C14082T, A14161G, G14162A, A14185T, G14198A, G14226A, T14308C, C14365G, T14386C, C14389T, A14417G, A14548G, C14562G, A14582G, A14693G, A14696G, A14750G, G15148A, G15315A, G1535A 79C, T15670C, A15758G, G16000A, T16075C, T16094C, G16145A, T16154C, C16173T, C16174T, A16183C, T16189C, C16214G, A16216G, A16235G, A16252C, A16254G, C16256T, A16258T, 16258ins-C, T16263C, A16265G, C16268T, T16288C, 16298ins-A, A16299G, A16316G, A16317G, T16342C, A16367C, T16368C, G16373A, T16381C, A16399G, C16400T, or at least two or more bases based on mutations. be able to.
According to the analysis of the present inventors, by confirming the presence or absence of 243 mutations which were not found in the 100-year-old group and were confirmed only in Parkinson's disease patients, the possibility that the person could become a Parkinson's disease patient Can be given as to whether or not the score is high.
[0014]
In the centenarian group, 519 mutations were confirmed. Of these mutations, one (one or more) of the 331 mutations commonly found in the 100-year-old group, or not found in the Parkinson's disease group but only in the 100-year-old group By detecting the 205 mutations, it is possible to provide data for determining whether the person becomes a long-lived person (or whether or not the person is likely to develop Parkinson's disease). The 126 mutations identified in both Parkinson's disease and centenarians are the most common mutations in centenarians.)
Thus, the third invention relates to human mitochondrial DNA in T63C, C64T, 66del-G, A93G, G94A, G103A, C151T, 190ins-A, A191G, C194T, T199C, A200G, A200G, A200G, A2G, A2G, A2A, G2A, A2G , C280T, A281G, 286del-A, 287del-A, 310ins-C, C348T, A351C, A368G, G380C, C382G, A385T, T408A, C456T, C481T, G499A, C506T, A533G, A546G, A663G, T681C, C752T, A856G , C983T, A998G, C1048T, T1107C, A1382 , T1420C, C1734T, A1736G, T1977C, 2150ins-A, A2706G, C2766T, T2887C, G3010A, 3106del-C, C3206T, T3338C, G3391A, T3456C, G3496T, A3520G, T3552A, G3591A, C3696T, A3768G, T3826C, G3882A, C3963A , C3970T, G4048A, T4062C, C4071T, C4086T, A4164G, T4248C, A4310G, T4612C, G4655A, G4649A, T4688C, T4705G, C4824G, C4824G, C4824G, A4824G, C4824G, A4824G. 01G, A5351G, C5379T, T5442C, G5460A, T5492C, A5539G, C5601T, T5628C, G5744A, T5788C, A5894G, T5964C, G5979A, C6053T, A6146G, C6242T, G6261A, A6299G, A6332G, G6383A, T6392C, A6416G, C6452T, C6455T, C6483T, T6512C, T6524C, C6542T, C6569A, T6641C, T6680C, A6698G, G6962A, A7146G, T7191C, C7244, T7270C, A7352T, A7352T, A7352T, A7352T, A7352T, A7352T, A7352T. T7738C, A7755G, C7810T, G7853A, C7868T, C7891T, T7961C, G8020A, A8021G, A8074G, C8140T, T8167C, C8203T, G8251A, T8265C, C8270T, G8290A, A8291G, G8392A, A8413G, C8414T, C8455T, C8461T, T8473C, A8489G, G8557A, G8557A, A8563G, A8563G, T8654C, A8784G, C8788T, C8794T, A8812G, C8829T, C8844T, C8964T, T9017C, C9069C, A9096C, C9069C, C9084C 80G, C9293T, C9296T, A9299G, A9341T, A9377G, T9479C, C9536T, A9545G, G9548A, T9750C, G9755A, G9804A, C9812T, T9824A, A9843G, T9950C, G9962A, C10104T, G10172A, T10274C, G10310A, T10345C, A10397G, A10398G, T10410C, T10609C, G10801A, A10876G, A10972G, C11059T, T11113C, C11146T, G11149A, C11151T, T11437C, C11536T, C11647T, C11665T, G1966T. , T11770C, T11944C, G11969A, G12007A, A12026G, A12040G, T12091C, G12192A, A12234G, T12354C, A12361G, C12405T, G12406A, T12408C, G12622A, G12630A, A12634G, G12651A, T12804C, T12811C, A12834G, C13011T, A13057G, C13110T, T13215C , A13221G, G13225A, C13251T, A13263G, A13269G, C13383T, A13413G, T13461C, A13563G, G13590A, A13606G, A13614G, T13617C. 651G, C13695A, G13708A, G13759A, G13810A, A13887G, G13928C, A14001G, A14002G, A14053G, A14133G, C14149T, C14158T, T14180C, T14200C, C14281G, T14287C, T14318C, T14470C, G14544A, A14605G, C14668T, C14867T, T14979C, C15223T, A15235G, A15236G, C15508T, A15524G, A15662G, A15724G, A15851G, G15884A, G15927A, 15940del-T, A15974G, A16037G, A16037G, A16037G 86C, T16093C, G16129A, T16140C, A16162G, C16169T, C16176T, C16201T, A16215G, T16224C, A16227G, A16240G, T16243C, C16257T, C16266A, A16269G, C16270T, C16278T, C16290T, C16291G, C16292T, C16292G, C16294T, C16296T, T16297C, A16302G, T16304C, A16309G, A16318T, G16319A, C16320T, C16327T, T16352C, C16355T, C16360T, T16362C, G16390A, G16456C. A gene based on a mutation in a human mitochondrial gene, which provides, based on a mutation in at least one or two or more of A16523G and C16527T, judgment data on whether or not the person becomes a long-lived person. It is a detection method. These 331 mutations are more frequent mutations in the centenarian group than in the Parkinson's disease group.
[0015]
In a fourth aspect, in the third aspect, in the human mitochondrial DNA, T63C, 66del-G, A93G, G94A, G103A, C151T, A191G, A210G, A257G, C280T, A281G, A286G, 286D-A281G , 310ins-C, C348T, A351C, A368G, G380C, C382G, A385T, C481T, C506T, A533G, A546G, A856G, C983T, A998G, T1420C, C1734T, T2887C, T3338C, T3456C, A3520G, T3552A, G3591A, C3696T, A3768G , T3826C, G3882A, C3963A, T4062C, A 4310G, T4612C, G4659A, T4688C, T4705C, C4850T, A5127G, C5379T, T5442C, T5492C, A5539G, T5628C, G5744A, T5788C, T5964C, G5979A, C6053T, A6146G, C6242T, G6261A, A6299G, A6332G, G6383A, A6416G, C6452T, C6483T, T6512C, T6524C, C6542T, C6569A, T6641C, A6698G, A7146G, T7191C, C7244T, T7270C, A7352T, T7389C, C772A, C7492, G7498A T, C7891T, T7961C, A8021G, A8074G, C8140T, T8167C, C8203T, T8265C, C8270T, G8290A, A8291G, G8392A, A8413G, C8455T, C8461T, A8489G, G8557A, G8557A, T8654C, A8784G, C8788T, A8812G, C8844T, T9017C, A9069G, T9084C, C9099A, C9129T, C9293T, A9299G, A9341T, T9479C, C9536T, A9545G, T9750C, G9804A, C9812T, A9843G, G992A, G98A, G992A, G9862A G, C11059T, T11113C, C11146T, G11149A, C11151T, T11437C, C11665T, G11696A, T11722C, T11770C, G11969A, A12040G, T12091C, G12192A, A12234G, T12354C, T12408C, G12622A, G12630A, A12634G, G12651A, T12804C, A12834G, C13011T, A13057G, T13215C, A13221G, G13225A, C13251T, A13263G, A13269G, C13383T, A13413G, T13461C, A13606G, A13614G, T13617A, C13695A 13810A, A13887G, A14001G, A14053G, C14149T, C14158T, C14281G, T14318C, G14544A, C14867T, A15235G, G15884A, 15940del-T, A15974G, A16037G, T16086C, C16169T, C16201T, A16215G, T16224C, A16240G, C16257T, C16266A, A16269G, C16270T, C16291G, C16292T, C16292G, C16296T, A16302G, A16318T, C16320T, C16327T, T16352C, C16355T, C16360T, G16456C, A1653. A method for detecting a gene based on a human mitochondrial gene mutation, the method comprising providing, based on a mutation of at least one or two or more bases of the above-mentioned 6527T, whether or not the person becomes a long-lived person. It is. These 205 mutations are mutations found only in the centenarian group.
[0016]
In addition, among all mutations, an appropriate ratio of “the number of polymorphisms observed in Parkinson's disease patients / the number of polymorphisms observed in centenarians (total of Gifu centennial and Tokyo centennial)” Range (eg, 1.2 or more, 1.5 or more, 2.0 or more, 3.0 or more, 0.8 or less, 0.7 or less, 0.6 or less, 0.5 or less, 0.4 or less, etc.) By selecting (exemplary), it is also possible to accurately give judgment data on the possibility that a certain person will have Parkinson's disease or the certain person will have a long life.
[0017]
BEST MODE FOR CARRYING OUT THE INVENTION
Next, an embodiment of the present invention will be described in detail with reference to the drawings, but the technical scope of the present invention is not limited by the following embodiment, without changing the gist, Various modifications can be made. Further, the technical scope of the present invention extends to an equivalent range.
[0018]
<Target>
The total nucleotide sequence of the mitochondrial genome (13 mRNA (protein coding region), 22 mRNAs in a group of 96 patients with Parkinson's disease and a group of centenarians (11 in the Gifu region and 85 in the Tokyo region) tRNA, and two rRNAs, see FIG. 1). All subjects agreed to participate in this study. This study was approved by the Ethics Committee of Nagoya University Comprehensive Health and Physical Education Center.
[0019]
<Method>
2 mL of venous blood was collected from each subject into blood collection tubes containing 50 mM EDTA. Total DNA was extracted from blood using MagExtractor System MFX-2000 (Toyobo, Osaka). All mitochondrial genomes are as previously reported (Masashi Tanaka, Mika Hayakawa, and Takayuki Ozawa, Automated Sequencing of 97, 11th, 19th, 1999, 24th, and 19th, 1995) Six fragments were amplified by PCR (polymerase chain reaction, 1st PCR), and then 60 regions overlapping each other were amplified by a second PCR (2nd PCR).
That is, the mitochondrial genome was amplified as a region (fragments AF) of about 3.0 kb by the PCR method using the primer pairs (L1 and H1 primers) shown in Table 1. The base sequences of the respective primers are as follows (in addition, among the primers described in Table 1, the base sequences of the respective primers except L5554, FL8053, FL8635, FL9213, FL12600, FL16221, H3082, H9235, H342) Are disclosed in the above-mentioned report, and are not described to avoid duplication.) L5545 is 5'-ACAGCTAAGGACTGCAAAC-3 '(SEQ ID NO: 1); FL8053 is 5'-TGTAAAACGACGGCAGTACAAGACGTCTTGCACTCAT-3' (SEQ ID NO: 2); 5'-TGTAAAACGACGGGCCAGTCACCAATCCACATGCCTATCA-3 '(SEQ ID NO: 4), FL12600: 5'-TGTAAAACGACGGGCCAGTTATTCATCCCTGGTAGCATTGT-3' (SEQ ID NO: 5) ), H3082 is 5'-TAGAAACCGACCTGGATCTAC-3 '(SEQ ID NO: 7), H9235 is 5'-TCATGGGCTGGGTTTTTACTA-3' (SEQ ID NO: 8), and H342 is 5'-TTTTTGGGGTTTGGCAGAGA-3 '(SEQ ID NO: 9). is there.
[0020]
[Table 1]

[0021]
The PCR method conditions were as follows: heat denaturation at 94 ° C. for 5 minutes, thermal denaturation at 94 ° C. for 15 seconds, annealing at 60 ° C. for 15 seconds, and extension reaction at 72 ° C. for 3 minutes for 40 cycles. An extension reaction was performed at 72 ° C. for 10 minutes. The 1st PCR amplification product was confirmed by electrophoresis on a 1% agarose gel and then visualized with ethidium bromide.
Thereafter, the fragments A to F were amplified by PCR using the primer pairs (FL2 and H2 primers) shown in Table 1 in 60 small regions of about 600 to 1000 bp (2nd PCR). The forward primer of 2nd PCR is an oligonucleotide of 38 bases, and a universal sequence primer (-21M13, 5'-TGTAAAACGACGGCGAGT-3 ') is located at the 5' end of the 20-chain L chain-specific sequence. It is obtained by binding 18 bases of the sequence of SEQ ID NO: 10). The conditions of the PCR method were as follows: thermal denaturation at 94 ° C. for 15 seconds, annealing at 60 ° C. for 15 seconds, and extension reaction at 72 ° C. for 3 minutes were performed for 40 cycles, followed by extension reaction at 72 ° C. for 10 minutes. These 2nd PCR DNAs were purified using MultiScreen-PCR plates (Millipore, Bedford, MA). The quality of the purified DNA was confirmed by 1.5% agarose gel electrophoresis containing ethidium bromide using a Ready-To-Run Separation Unit (Amersham Pharmacia Biotech AB, San Francisco, Calif.).
[0022]
The sequencing reaction was carried out using 2nd PCR DNA, -21M13 universal primer, and BigDye Terminator Cycle Sequence Ready Reaction Kit 1.0 or 3.0 (Applied Biosystems, Foster City, CA). The PCR conditions were as follows: heat denaturation at 96 ° C. for 5 minutes, then heat denaturation at 96 ° C. for 10 seconds, annealing at 50 ° C. for 5 seconds, and extension reaction at 62 ° C. for 3 minutes for 25 cycles. An extension reaction was performed at 62 ° C. for 3 minutes. After the sequencing reaction, excess Dye Terminator was removed by gel filtration using a MultiScreen-PCR HV plate (Millipore). The purified DNA sample was dried, and then dissolved in template replacement reagent (TSR, Applied Biosystems) or formamide (Applied Biosystems). The lysed DNA sample was heat denatured at 95 ° C. for 2 minutes and immediately transferred to ice. DNA sequencing was analyzed using an automated DNA sequencer 310 or 377 (Applied Biosystems).
The sequence analysis was performed using Sequencing Analysis Program version 4.1 (Applied Biosystems). The sequence fragments were aligned using the sequence analysis software Sequencher 3.1.1 (Gene Codes, Ann Arbor, MI) to identify the location of the single nucleotide polymorphism (hereinafter, referred to as “SNP” (single nucleotide polymorphisms)). It was used for. Each SNP was reconfirmed visually. In addition, since amplification of DNA overlapped with each other, each SNP was confirmed in at least two regions.
[0023]
Each mtDNA sequence was identified by the original Cambridge Reference Sequence (oCRS) and the revised Cambridge Reference Sequence (rCRS) (Andrews RM, Kubacka I., Chinney PF, Lighttowers RN, Turnbull DM. , Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet 1999; 23: 147.).
[0024]
<Result>
1. Consensus sequence in Japanese (Japanese Consensus sequence (JCS))
In this study, SNPs were analyzed by comparison with rCRS. When the frequency was 100% or close to that, the nucleotide sequence was used as a consensus sequence (JCS) in Japanese and used as a standard nucleotide sequence (Table 2).
[0025]
[Table 2]

[0026]
2. About the number of base substitutions, insertions, and deletions
In 96 Parkinson's disease patients, 557 polymorphisms were found throughout the mitochondrial genome, and there were 348 polymorphisms in the protein coding region. Of these, 244 (70.1%) were synonymous substitutions (base substitutions not involving amino acid substitutions), and 104 (29.9%) were nonsynonymous substitutions (base sequence). With amino acid substitution). Base substitutions (substitutions, insertions, and deletions) between two rRNAs and 22 tRNAs were observed at 73 sites. Furthermore, in the non-coding region, polymorphisms were found at 136 locations.
In 96 perpetrators, 519 polymorphisms were found in the entire mitochondrial genome, and 327 polymorphisms were found in the protein coding region. Of these, 231 (70.6%) were synonymous substitutions, and 96 (29.4%) were non-synonymous substitutions. In addition, base mutations (substitutions, insertions, and deletions) of two rRNAs and 22 tRNAs were observed at 56 positions. Furthermore, in the non-coding region, polymorphism was found at 135 sites, and there was one polymorphism in the L chain replication initiation region.
[0027]
Tables 3 to 22 show all the mutations (substitutions, insertions, and deletions) found in Parkinson's disease patients and centenarians in the coding region, the RNA gene region, and the non-coding region.
(1) Tables 3 to 10 show the comparison of the frequencies of synonymous substitutions occurring between the Parkinson's disease patient group and the centenarian group in the protein coding region.
[0028]
[Table 3]

[0029]
[Table 4]

[0030]
[Table 5]

[0031]
[Table 6]

[0032]
[Table 7]

[0033]
[Table 8]

[0034]
[Table 9]

[0035]
[Table 10]

[0036]
(2) The frequency of non-synonymous substitution in the protein coding region is shown in Tables 11 to 14.
[Table 11]

[0037]
[Table 12]

[0038]
[Table 13]

[0039]
[Table 14]

[0040]
(3) Tables 15 to 17 show base substitutions in two rRNAs and 22 tRNAs detected from both the Parkinson's disease patient group and the centenarian group.
[Table 15]

[0041]
[Table 16]

[0042]
[Table 17]

[0043]
(4) Major non-coding region, L-chain replication region (origin of L-strand replication), and minor non-coding region (Major non-coding region) detected from both the Parkinson's disease patient group and the centenarian group Table 18 to Table 22 show the base substitution in the Minor non-coding region).
[Table 18]

[0044]
[Table 19]

[0045]
[Table 20]

[0046]
[Table 21]

[0047]
[Table 22]

[0048]
3. Base substitution at the start of L chain replication
G5744A was observed in the vicinity of the light chain replication origin in one centenarian (Table 19).
In addition, if necessary, from these tables, mutations found only in the Parkinson's disease group, mutations found more frequently in the Parkinson's disease group than in the 100-life group, mutations found only in the 100-life group, In addition, mutations that are observed more frequently in the group of centenarians than in the group of Parkinson's disease (further, of those mutations, synonymous substitution or non-synonymous substitution) can be easily extracted.
As described above, according to the present embodiment, it is useful to determine whether (1) a certain person may have Parkinson's disease, or (2) whether a certain person may have a healthy longevity. And a gene detection method that gives important information. Further, according to the present embodiment, it is possible to provide a method for performing personal identification in an appropriate field.
[0049]
[Sequence list]

[Brief description of the drawings]
FIG. 1 is a diagram showing the arrangement of human mitochondrial DNA genes.

Claims

In human mitochondrial DNA, 42ins-C, T63C, C64T, 66del-G, G68A, A73G, A93G, G94A, G103A, T131C, T146C, C150T, C15T, A, G, A, G, A, G, A, G, A, G, A, G, A, G, A , A193G, C194T, T195C, T196C, C198T, T199C, A200G, A202G, G203A, T204C, G207A, A210G, A211G, A214G, G228A, A235G, 248del-A, T252C, A257G, G260A, A263G, T279C, C280 , A281G, A284G, 286del-A, 287del-A, C298T, 310ins-C, C325T, C348G, C348T, A351C, A368G, G380C, T380G, C380G, T380G, T380G, T380G , T489C, G499A, T504C, C506T, G513A, C530T, A533G, 540ins-C, A546G, C552T, A663G, T681C, G709A, C752T, A827G, A856G, T961C, C983T, C984T, A998G, A1041G, C1048T , T1107C, A1118G, T1119C, A1148G, G1211A, C1310T, A1382C, T1420C, A1438G, G1442A, G1598A, G1664A, G1709A, G1719A, C1734T, A1736G, T1819C, T1822C, G1888A, T1977C, 2150ins-A, A2178G, A2220G, A2246G , C2263A, T2330C, T2416C, T2626C, A2706G, C2766T, C2772T, G2831A, C2835T, T2863C, T2887C, G3010A, 3106del-C, 3107del- , C3204T, C3206T, A3221G, T3278C, G3316A, A3327G, T3336C, T3338C, G3391A, T3394C, A3397G, T3423C, C3442T, T3456C, G3496T, C3497T, A3520G, A3537G, T3552C, T3552A, G3591A, T3644C, C3696T, A3720G, A3759G , A3768G, T3826C, A3873G, G3882A, C3960T, C3963A, C3970T, T4047C, G4048A, T4062C, C4071T, C4086T, G4092A, T4113A, T4113A. , A4131G, A4164G, A4203G, T4209C, T4232C, T4248C, C4251T, A4310G, A4343G, T4386C, C4394T, G4491A, C4505T, G4541T, T4612C, G4655A, G4659A, C4670T, T4688C, T4705C, A4715G, A4732G, T4736C, T4742C, A4769G , A4793G, G4820A, A4824G, A4833G, C4850T, T4859C, C4883T, A4895G, G4924A, C4926T, A4958G, T5048C, C5049T, G5054A. , A5127G, A5128G, G5147A, A5153G, C5178A, T5201C, G5231A, G5237A, A5240G, G5261A, C5263T, A5301G, A5351C, A5351G, C5379T, G5417A, A5441G, T5442C, G5460A, T5465C, G5471A, T5492C, A5539G, C5601T, T5628C , T5655C, G5744A, G5773A, T5788C, G5821A, T5826C, T5826C, A5894G, A5900C, A5951G, T5964C, G5979A, G6018A, G6023A , A6039G, C6053T, A6146G, G6179A, T6185C, T6221C, C6242T, T6253C, G6261A, T6278C, A6299G, G6305A, A6332G, G6383A, T6392C, C6410T, T6413C, A6416G, C6452T, C6455T, C6483T, T6512C, T6524C, A6533G, C6542T , C6569A, A6575G, T6614C, T6620C, T6641C, C6644T, T6671C, T6680C, C6689T, A6698G, T6719C, A6737G, A6752G, C6761T. , G6962A, C6983T, C7028T, T7058C, T7142C, A7146G, T7191C, C7196A, C7214T, T7220C, C7232T, C7235T, C7244T, C7256T, T7258C, T7270C, A7352T, T7389C, A7403G, C7492T, 7502del-C, G7521A, G7598A, G7600A , A7673G, T7684C, T7738C, A7755G, C7774T, C7810T, A7822G, G7853A, T7861C, C7867T, C7868T, C7891T, C7909T, T7912A, C7912A, C7912T, C7912A 61C, G8020A, A8021G, T8063C, A8071G, A8074G, C8140T, A8149G, T8167A, T8167C, A8188G, T8200C, C8203T, G8206A, A8225G, T8227C, G8251A, T8265C, C8270T, G8290A, A8291G, C8297G, A8308G, T8383C, G8392A, A8413G, C8414T, T8419C, C8429A, T8450C, C8455T, C8461T, A8470G, T8473C, A8489G, A8537G, A8537G, G8557A, G8557A, A8563A. 63G, G8572A, G8584A, C8595T, T8610C, T8654C, A8664G, C8684T, A8701G, T8762C, A8784G, C8788T, C8794T, A8812G, C8829T, C8844T, G8854A, A8860G, A8894T, C8905A, A8929G, C8964T, G8994A, T9017C, A9041G, G9053A, A9069G, T9084C, T9090C, C9099A, A91115G, G9123A, T9128C, C9129T, T9165C, T9174C, A9180G, A9242G, A9288G, C9288G, C9288G, C9288G, C9288G 96T, A9299G, G9305A, A9341T, A9377G, T9386C, C9431T, G9477A, T9479C, A9494G, C9536T, T9540C, A9545G, G9548A, G9575A, G9612A, A9667G, T9750C, G9755A, G9804A, C9812T, T9824C, T9824A, T9833C, T9836G, A9843G, G9921A, G9932A, T9938C, T9950C, T9959C, G9962A, T9977C, T10084C, C10104T, G10172A, C10181T, T10238C, T10274C. 0A, T10345C, G10373A, A10397G, A10398G, C10400T, T10410C, A10411G, T10609C, C10637T, G10646A, A10750G, T10790C, G10801A, T10873C, A10876G, T10915C, C10954T, A10972G, C10976T, G11016A, T11017C, A11020G, C11059T, A11084G, T11087C, T11113C, C11146T, G11149A, C11151T, A11167G, C11215T, T11437C, A11530G, C11536T, C11647T, C1 665T, G11696A, T11701C, G11719A, T11722C, T11770C, T11854C, G11914A, T11944C, A11959G, G11969A, G12007A, A12026G, A12030G, A12040G, C12084T, C12088T, T12091C, C12092A, G12192A, A12210G, A12234G, T12311C, T12354C, A12358G, A12361G, G12372A, T12396C, A12397G, C12405T, G12406A, T12408C, T12468C, G12622A, G12630A, C12633T, A12634G, G12651C, G12651A, C12705T, G12771A, T12804C, T12811C, C12816T, A12834G, T12880C, C12882T, C13011T, A13050G, C13053G, A13057G, A13104G, A13105G, C13110T, G13135A, T13143C, T13215C, A13221G, T13224C, G13225A, C13251T, A13263G, A13269G, A13278G, T13281C, C13338T, G13359A, C13383T, A13395G, A13413G, A13434G, T13461 , T13500C, A13563G, G13590A, A13606G, A13614G, T13617C, A13629G, A13651G, C13695A, G13708A, G13759A, T13768C, G13810A, A13827G, T13879C, A13887G, G13928A, G13928C, A14001G, A14002G, G14016A, A14053G, C14082T, A14091G, A14133G , C14149T, C14158T, A14161G, G14162A, T14180C, A14185T, G14198A, T14200C, G14226A, C14281T, C14 81G, T14287C, T14308C, T14318C, T14325C, G14364A, C14365G, T14371C, T14386C, C14389T, A14417G, T14470C, G14476A, G14544A, A14548G, C14562G, G14569A, A14582G, A14605G, C14668T, A14693G, A14696G, A14750G, C14766T, T14783C, C14867T, C14944T, T14979C, G15043A, T15067C, G15148A, A15218G, C15223T, A15235G, A15236G, G15301A, G 15314A, G15323A, A15326G, C15331A, G15346A, G15355A, T15440C, T15479C, A15487T, G15497A, C15508T, C15518T, A15524G, C15535T, A15662G, T15670C, A15724G, A15758G, T15784C, T15850C, A15851G, A15860G, A15874G, G15884A, A15924G, G15927A, T15940-, T15941C, A15951G, A15954G, A15974G, G16000A, A16037G, A16051G, T16075C, T16086C , T16092C, T16093C, T16094C, C16111T, T16126C, G16129A, T16136C, T16140C, G16145A, T16154C, A16162G, A16164G, C16168T, C16169T, T16172C, C16173T, C16174T, C16176T, A16183C, T16189C, C16201T, T16209C, C16214G, A16215G, A16216G , T16217C, C16223T, T16224C, A16227G, C16232A, C16234T, A16235G, A16240G, T16243C, G16244A, C1624 5T, T16249C, A16252C, A16254G, C16256T, C16257A, C16257T, A16258T, 16258ins-C, C16260T, C16261T, T16263C, A16265G, C16266T, C16266A, C16268T, A16269G, C16270T, G16274A, C16278T, A16284G, C16287T, T16288C, C16290T, C16291T, C16291G, C16292T, C16292G, C16294T, C16295T, C16296T, T16297C, 16298ins-A, T16298C, A16299G, A1630 G, A16302G, T16304C, A16309G, T16311C, A16316G, A16317G, A16318T, G16319A, C16320T, T16324C, T16325C, C16327T, T16342C, C16344T, T16352C, C16355T, T16356C, T16357C, C16360T, T16362C, A16367C, T16368C, G16373A, T16381C, G16390A, A16399G, C16400T, G16456C, A16463G, A16497G, T16519C, A16523G, C16527T, or at least two or more base changes. An individual identification method based on human mitochondrial gene mutation, characterized in that individuals are identified based on differences.

In human mitochondrial DNA, 42ins-C, C64T, G68A, A73G, T131C, T146C, C150T, T152C, A153G, A183G, G185A, A19G, T19, C19, A19G, A19G, A19G, A19G, A19G, A19G , G203A, T204C, G207A, A211G, A214G, G228A, A235G, 248del-A, T252C, G260A, A263G, T279C, A284G, C40T, C40G, C40T, C340G 456T, T489C, G499A, T504C, G513A, C530T, 540ins-C, C552T, A663G, T681C, G709A, C752T, A827G, T961C, C984T, A1041G, C1048T, T1107C, A1118G, T1119C, A1148G, G1211A, C1310T, A1382C, A1438G, G1442A, G1598A, G1664A, G1709A, G1719A, A1736G, T1819C, T1822C, G1888A, T1977C, 2150ins-A, A2T2A, A2230G, A2220G, A2220G 2416C, T2626C, A2706G, C2766T, C2772T, G2831A, C2835T, T2863C, G3010A, 3106del-C, 3107del-C, A3145G, C3204T, C3206T, A3221G, T3278C, G3316A, A3327G, T3336C, G3391A, T3394C, A3397G, T3423C, C3442T, G3496T, C3497T, A3537G, T3552C, T3644C, A3720G, A3759G, A3873G, C3960T, C3970T, T4047C, G4048A, C4071T, C4072T, C4096G 3A, T4117C, A4131G, A4164G, A4203G, T4209C, T4232C, T4248C, C4251T, A4343G, T4386C, C4394T, G4491A, C4505T, G4541T, G4655A, C4670T, A4715G, A4732G, T4736C, T4742C, A4769G, A4793G, G4820A, A4824G, A4833G, T4859C, C4883T, A4895G, G4924A, C4926T, A4958G, T5048C, C5049T, G5054A, T5108C, A5128G, G5147A, A5153G, C5153G 1C, G5231A, G5237A, A5240G, G5261A, C5263T, A5301G, A5351G, A5351C, G5417A, A5441G, G5460A, T5465C, G5471A, C5601T, T5655C, G5773A, G5821A, T5826C, T5826C, A5894G, A5900C, A5951G, G6018A, G6023A, G6026A, A6039G, G6179A, T6185C, T6221C, T6253C, T6278C, G6305A, T6392C, C6410T, T6413C, C6455T, A6533G, A6575G, A6575G, A6575G. 0C, C6644T, T6671C, T6680C, C6689T, T6719C, A6737G, A6752G, C6761T, G6899A, G6962A, C6983T, C7028T, T7058C, T7142C, C7196A, C7214T, T7220C, C7232T, C7235T, C7256T, T7258C, A7403G, 7502del-C, G7521A, G7600A, A7673G, T7684C, C7774T, A7822G, G7853A, T7861C, C7867T, C7909T, G7912A, C7927T, G8020A, T8063C, A8063C, A8063C, A8063C 8167A, A8188G, T8200C, G8206A, A8225G, T8227C, G8251A, C8297G, A8308G, T8383C, C8414T, T8419C, C8429A, T8450C, A8470G, T8473C, A8537G, A8537G, A8563G, A8563G, G8572A, G8584A, C8595T, T8610C, A8664G, C8864T, A8701G, T8762C, C8794T, C8829T, G8854A, A8860G, A8894T, C8905A, A8929G, C8964T, G8994A, A9041G, G9053C, T90C. 9115G, G9123A, T9128C, T9165C, T9174C, A9180G, A9242G, A9288G, C9296T, G9305A, A9377G, T9386C, C9431T, G9477A, A9494G, T9540C, G9548A, G9575A, G9612A, A9667G, G9755A, T9824C, T9824A, T9833C, T9836G, G9921A, G9932A, T9938C, T9950C, T9959C, T9977C, T10084C, C10104T, C10181T, T10238C, G10310A, T10345C, G10373A, A10397G, 10398G, C10400T, T10410C, A10411G, T10609C, C10637T, G10646A, A10750G, T10790C, G10801A, T10873C, T10915C, C10954T, C10976T, G11016A, T11017C, A11020G, A11084G, T11087C, A11167G, C11215T, A11530G, C11536T, C11647T, T11701C, G11719A, T11854C, G11914A, T11944C, A11959G, G12007A, A12026G, A12030G, C12084T, C12088T, C12092A , A12210G, T12311C, A12358G, A12361G, G12372A, T12396C, A12397G, C12405T, G12406A, T12468C, C12633T, G12651C, C12705T, G12771A, T12811C, C12816T, T12880C, C12882T, A13050G, C13053G, A13104G, A13105G, C13110T, G13135A, T13143C , T13224C, A13278G, T13281C, C13338T, G13359A, A13395G, A13434G, T13500C, A13563G, G13590A, A136 9G, A13651G, G13708A, G13759A, T13768C, A13827G, T13879C, G13928C, G13928A, A14002G, G14016A, C14082T, A14091G, A14133G, A14161G, G14162A, T14180C, A14185T, G14198A, T14200C, G14226A, C14281T, T14287C, T14308C, T14325C, G14364A, C14365G, T14371C, T14386C, C14389T, A14417G, T14470C, G14476A, A14548G, C14562G, G14569A, A1 4582G, A14605G, C14668T, A14693G, A14696G, A14750G, C14766T, T14783C, C14944T, T14979C, G15043A, T15067C, G15148A, A15218G, C15223T, A15236G, G15301A, G15314A, G15323A, A15326G, C15331A, G15346A, G15355A, T15440C, T15479C, A15487T, G15497A, C15508T, C15518T, A15524G, C15535T, A15662G, T15670C, A15724G, A15758G, T15784C, T15850C, A15851G, A15860G, A15874G, A15924G, G15927A, T15941C, A15951G, A15954G, G16000A, A16051G, T16075C, T16092C, T16093C, T16094C, C16111T, T16126C, G16129A, T16136C, T16140C, G16145A, T16154C, A16162G, A16164G, C16168T, T16172C, C16173T, C16174T, C16176T, A16183C, T16189C, T16209C, C16214G, A16216G, T16217C, C16223 T, A16227G, C16232A, C16234T, A16235G, T16243C, G16244A, C16245T, T16249C, A16252C, A16254G, C16256T, C16257A, A16258T, 16258ins-C, C16260T, C16261T, T16263C, A16265G, C16266T, C16268T, G16274A, C16278T, A16284G, C16287T, T16288C, C16290T, C16291T, C16294T, C16295T, T16297C, T16298C, 16298ins-A, A16299G, A16300G, T16304 At least one of A16309G, T16311C, A16316G, A16317G, G16319A, T16324C, T16325C, T16342C, C16344T, T16356C, T16357C, T16362C, A16367C, T16368C, G16373A, T16381C, G16390A, A16399G, C16400T, A16463G, A16497G, among T16519C Or a method for detecting a gene based on a mutation in a human mitochondrial gene, which is based on a mutation in two or more bases and provides information on whether or not the person has Parkinson's disease.

In human mitochondrial DNA, T131C, T146C, C150T, A153G, A189G, T195C, G207A, A214G, C298T, C431T, G709A, A827G, T1119C, A1438G, G1719A, G1888A, T2626C, C2772T, T3394C, C3497T, T4386C, A4715G, A4732G , A4793G, A4833G, T4859C, A4895G, A4958G, C5049T, T5108C, G5147A, G5231A, G5417A, T5465C, G5773A, T6185C, T6185C, T6185T, C6106C 2G, C7028T, C7196A, C7867T, T8200C, A8701G, T9090C, G9123A, T9540C, C10181T, G10373A, C10400T, T10873C, C10976T, T11017C, A11084G, C11215T, G11719A, G11914A, A12358G, G12372A, C12705T, G12771A, T12880C, A13104G, G14364A, T14371C, G14476A, G14569A, T14783C, G15043A, T15067C, G15301A, G15323A, T15440C, A15487T, G15497A, 15535T, T15784C, T15850C, A15860G, A15874G, T15941C, A15951G, A15954G, T16092C, C16111T, T16126C, T16209C, T16217C, C16223T, C16232A, C16234T, G16244A, C16257A, C16260T, C16261T, G16274A, C16287T, C16291T, T16298C, T16324C, 3. The method according to claim 2, wherein the determination data is given based on a mutation of at least one or two or more of T16325C, A16463G, and A16497G to determine whether the person has Parkinson's disease. 4. Gene detection method based on human mitochondrial gene mutation of the mounting.

In human mitochondrial DNA, 42ins-C, A183G, G185A, A193G, T196C, C198T, G203A, A211G, G228A, T252C, T279C, A284G, C325T, C348G, T408G, C441T, 451ins-T, T504C, G513A, C530T, 540ins -C, C552T, T961C, C984T, A1041G, A1118G, G1211A, G1664A, G1709A, T1819C, T1822C, A2178G, A2220G, C2263C, T2316C, T2330C, T2330C, T2330C G, C3204T, A3221G, A3327G, T3336C, A3397G, T3423C, C3442T, T3552C, T3644C, A3720G, A3873G, C3960T, T4047C, G4092A, G4113A, A4131G, A4203G, T4232C, C4251T, G4491A, G4541T, C4670T, T4736C, T4742C, G4924A, C4926T, T5048C, G5054A, A5128G, T5201C, G5237A, A5240G, G5261A, C5263T, A5351C, A5441G, G5471A, T5651C, T5651C, T5651C, T5651C. C, T5826C, A5900C, A5951G, G6026A, A6039G, G6179A, T6278C, G6305A, A6533G, A6575G, T6614C, C6644T, T6671C, T6719C, C6761T, G6899A, C6983T, T7058C, T7142C, C7214T, T7220C, C7235T, T7258C, 7502del- C, A7673G, C7774T, T7861C, C7909T, C7927T, T8063C, A8149G, T8167A, A8188G, A8225G, T8227C, C8297G, A8308C, T8319C, T8319C. 429A, A8470G, A8537G, A8537G, G8572A, C8595T, T8610C, A8664G, C8684T, G8854A, A8894T, C8905A, A8929G, A9041G, A9115G, T9174C, A9242G, A9288G, G9305A, T9386C, C9431T, G9477A, G9612A, T9833C, T9836G, G9921A, G9932A, T9938C, T9959C, T9977C, T10084C, T10238C, A10411G, C10637T, G10646A, A10750G, T10790C, T10915C, C10954T, 11016A, A11020G, T11087C, A11167G, A11530G, T11701C, T11854C, A11959G, A12030G, C12084T, C12092A, A12210G, T12396C, A12397G, T12468C, C12633T, C12816T, A13050G, C13053G, T13143C, T13224C, T13281C, C13338T, G13359A, A13395G, A13434G, T13500C, A13629G, T13879C, G14016A, C14082T, A14161G, G14162A, A14185T, G14198A, G14226A , T14308C, C14365G, T14386C, C14389T, A14417G, A14548G, C14562G, A14582G, A14693G, A14696G, A14750G, G15148A, G15314A, G15355A, T15479C, T15670C, A15758G, G16000A, T16075C, T16094C, G16145A, T16154C, C16173T, C16174T, A16183C , T16189C, C16214G, A16216G, A16235G, A16252C, A16254G, C16256T, A16258T, 16258ins-C, T16263C, A 6265G, C16268T, T16288C, 16298ins-A, A16299G, A16316G, A16317G, T16342C, A16367C, T16368C, G16373A, T16383C, and at least one of the bases of at least two mutations, G16373A, T16381C. 3. The method for detecting a gene based on a human mitochondrial gene mutation according to claim 2, wherein judgment data on whether or not the disease causes Parkinson's disease is provided.

In human mitochondrial DNA, T63C, C64T, 66del-G, A93G, G94A, G103A, C151T, 190ins-A, A191G, C194T, T199C, A200G, T204G, A210G, A210G, A210G, A210G, A210G, A210G, A210G , 287del-A, 310ins-C, C348T, A351C, A368G, G380C, C382G, A385T, T408A, C456T, C481T, G499A, C566T, A533G, A835G , T1107C, A1382C, T1420C, C1734T, A1736G, T1977C, 2150ins-A, A2706G, C2766T, T2887C, G3010A, 3106del-C, C3206T, T3338C, G3391A, T3456C, G3496T, A3520G, T3552A, G3591A, C3696T, A3768G, T3826C , G3882A, C3963A, C3970T, G4048A, T4062C, C4071T, C4086T, A4164G, T4248C, A4310G, T4612C, G4655A, G4659A, T4688C, T4688C, T4688C, T4688C, T4688C, T4688C. C4850T, C4883T, A5127G, A5153G, C5178A, A5301G, A5351G, C5379T, T5442C, G5460A, T5492C, A5539G, C5601T, T5628C, G5744A, T5788C, A5894G, T5964C, G5979A, C6053T, A6146G, C6242T, G6261A, A6299G, A6332G, G6383A, T6392C, A6416G, C6452T, C6455T, C6483T, T6512C, T6524C, C6542T, C6569A, T6641C, T6680C, A6698G, G6962A, A7166A. T7191C, C7244T, T7270C, A7352T, T7389C, A7403G, C7492T, G7598A, T7684C, T7738C, A7755G, C7810T, G7853A, C7868T, C7891T, T7961C, G8020A, A8021G, A8074G, C8140T, T8167C, C8203T, G8251A, T8265C, C8270T, G8290A, A8291G, G8392A, A8413G, C8414T, C8455T, C8461T, T8473C, A8489G, G8557A, G8557A, A8563G, A8563G, T8654C, 8764C. C8788T, C8794T, A8812G, C8829T, C8844T, C8964T, T9017C, A9069G, T9084C, C9099A, C9129T, T9165C, A9180G, C9293T, C9296T, A9299G, A9341T, A9377G, T9479C, C9536T, A9545G, G9548A, T9750C, G9755A, G9804A, C9812T, T9824A, A9843G, T9950C, G9962A, C10104T, G10172A, T10274C, G10310A, T10345C, A10397G, A10398G, T10410C, T10609C. G10801A, A10876G, A10972G, C11059T, T11113C, C11146T, G11149A, C11151T, T11437C, C11536T, C11647T, C11665T, G11696A, T11722C, T11770C, T11944C, G11969A, G12007A, A12026G, A12040G, T12091C, G12192A, A12234G, T12354C, A12361G, C12405T, G12406A, T12408C, G12622A, G12630A, A12634G, G12651A, T12804C, T12811C, A12834G, C1301 T, A13057G, C13110T, T13215C, A13221G, G13225A, C13251T, A13263G, A13269G, C13383T, A13413G, T13461C, A13563G, G13590A, A13606G, A13614G, T13617C, A13651G, C13695A, G13708A, G13759A, G13810A, A13887G, G13928C, A14001G, A14002G, A14053G, A14133G, C14149T, C14158T, T14180C, T14200C, C14281G, T14287C, T14318C, T14470C, G14 544A, A14605G, C14668T, C14867T, T14979C, C15223T, A15235G, A15236G, C15508T, A15524G, A15662G, A15724G, A15851G, G15884A, G15927A, 15940del-T, A15974G, A16037G, A16051G, T16086C, T16093C, G16129A, T16140C, A16162G, C16169T, C16176T, C16201T, A16215G, T16224C, A16227G, A16240G, T16243C, C16257T, C16266A, A16269G, C16270 , C16278T, C16290T, C16291G, C16292T, C16292G, C16294T, C16296T, T16297C, A16302G, T16304C, A16309G, A16318T, G16319A, C16320T, C16327T, T16352C, C16355T, C16360T, T16362C, G16390A, G16456C, T16519C, A16523G, out of C16527T A method for detecting a gene based on a mutation in a human mitochondrial gene, the method comprising providing, based on at least one or two or more base mutations, judgment data on whether or not the person becomes a long-lived person.

In human mitochondrial DNA, T63C, 66del-G, A93G, G94A, G103A, C151T, A191G, A210G, A257G, C280T, A281G, 286del-A, 287del-A, 287del-A, 287del-A, 287del-A, 287del-G , A385T, C481T, C506T, A533G, A546G, A856G, C983T, A998G, T1420C, C1734T, T2887C, T3338C, T3456A, T3456A, G, A3520G, A3520G, A3520C, A3520G 062C, A4310G, T4612C, G4659A, T4688C, T4705C, C4850T, A5127G, C5379T, T5442C, T5492C, A5539G, T5628C, G5744A, T5788C, T5964C, G5979A, C6053T, A6146G, C6242T, G6261A, A6299G, A6332G, G6383A, A6416G, C6452T, C6483T, T6512C, T6524C, C6542T, C6569A, T6641C, A6698G, A7146G, T7191C, C7244T, T7270C, A7352T, T7389T, C7492T. 598A, T7738C, A7755G, C7810T, C7868T, C7891T, T7961C, A8021G, A8074G, C8140T, T8167C, C8203T, T8265C, C8270T, G8290A, A8291G, G8392A, A8413G, C8455T, C8461T, A8489G, G8557A, G8557A, T8654C, A8784G, C8788T, A8812G, C8844T, T9017C, A9069G, T9084C, C9099A, C9129T, C9293T, A9299G, A9341T, T9479C, C9536T, A9545G, T9750C 804A, C9812T, A9843G, G9962A, G10172A, T10274C, A10876G, A10972G, C11059T, T11113C, C11146T, G11149A, C11151T, T11437C, C11665T, G11696A, T11722C, T11770C, G11969A, A12040G, T12091C, G12192A, A12234G, T12354C, T12408C, G12622A, G12630A, A12634G, G12651A, T12804C, A12834G, C13011T, A13057G, T13215C, A13221G, G13225A, C13 51T, A13263G, A13269G, C13383T, A13413G, T13461C, A13606G, A13614G, T13617C, C13695A, G13810A, A13887G, A14001G, A14053G, C14149T, C14158T, C14281G, T14318C, G14544A, C14867T, A15235G, G15884A, 15940del-T, A15974G, A16037G, T16086C, C16169T, C16201T, A16215G, T16224C, A16240G, C16257T, C16266A, A16269G, C16270T, C16291G , C16292T, C16292G, C16296T, A16302G, A16318T, C16320T, C16327T, T16352C, C16355T, C16360T, G16456C, A16523G, C16527T or at least one of the following: The method for detecting a gene based on a mutation in a human mitochondrial gene according to claim 5, wherein a judgment data on whether or not the gene is obtained is given.